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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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Review Article

Diabetes Mellitus and Energy Dysmetabolism in Alzheimer’s Disease: Understanding the Relationships and Potential Therapeutic Targets

Author(s): Adejoke Y. Onaolapo, Folusho O. Ojo, Olufunto O. Adeleye, Joshua Falade and Olakunle J. Onaolapo*

Volume 19, Issue 8, 2023

Published on: 14 February, 2023

Article ID: e020123212333 Pages: 15

DOI: 10.2174/1573399819666230102141154

Price: $65

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Abstract

Over the last century, there has been a gradual but sustained increase in life expectancy globally. A consequence of increased life expectancy is an associated rise in the prevalence of agerelated chronic debilitating neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, and multiple sclerosis. These disorders, which are generally characterised by the loss of motor/sensory neurons and cognitive decline, have continued to confound researchers who are working tirelessly to define their pathogenetic mechanisms and develop effective therapies. In the last few years, there has been increasing evidence of the existence of a relationship between energy metabolism and neurodegeneration, with reports that type 2 diabetes mellitus increases the risk of AD. Evidence from preclinical and epidemiologic studies has associated dysmetabolism and dysmetabolic syndromes with the development of neurodegenerative changes. More recently, diabetes mellitus and energy dysmetabolism have been linked to the aetiopathogenesis of AD. Moreover, metabolic hormones, including ghrelin, leptin, insulin, and insulin-like growth factor (IGF)-1, have been reported to play key roles in the regulation of neuronal injury and loss in neurodegenerative diseases like AD. In this narrative review, we examine the current scientific evidence regarding the role of dysmetabolism (including diabetes mellitus and metabolic syndrome) in AD and how it impacts disease progression and the development of novel therapies in AD.

[1]
Global health Observatory. Global Health Estimate: Life expectancy and the leading causes of death and mortality. In: World Health Organisation. Geneva 2021.
[2]
Hou Y, Dan X, Babbar M, et al. Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 2019; 15(10): 565-81.
[http://dx.doi.org/10.1038/s41582-019-0244-7] [PMID: 31501588]
[3]
Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 2017; 9(7): a028035.
[http://dx.doi.org/10.1101/cshperspect.a028035] [PMID: 28062563]
[4]
Procaccini C, Santopaolo M, Faicchia D, et al. Role of metabolism in neurodegenerative disorders. Metabolism 2016; 65(9): 1376-90.
[http://dx.doi.org/10.1016/j.metabol.2016.05.018] [PMID: 27506744]
[5]
Chen Z, Zhong C. Decoding Alzheimer’s disease from perturbed cerebral glucose metabolism: Implications for diagnostic and therapeutic strategies. Prog Neurobiol 2013; 108: 21-43.
[http://dx.doi.org/10.1016/j.pneurobio.2013.06.004] [PMID: 23850509]
[6]
Cai Z, Xiao M, Chang L, Yan LJ. Role of insulin resistance in Alzheimer’s disease. Metab Brain Dis 2015; 30(4): 839-51.
[http://dx.doi.org/10.1007/s11011-014-9631-3] [PMID: 25399337]
[7]
Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease. J Neurosci Res 2017; 95(4): 943-72.
[http://dx.doi.org/10.1002/jnr.23777] [PMID: 27350397]
[8]
Berlanga-Acosta J, Guillén-Nieto G, Rodríguez-Rodríguez N, et al. Insulin resistance at the crossroad of Alzheimer disease pathology: A review. Front Endocrinol 2020; 11: 560375.
[http://dx.doi.org/10.3389/fendo.2020.560375] [PMID: 33224105]
[9]
Błaszczyk JW. Energy metabolism decline in the aging brain-pathogenesis of neurodegenerative disorders. Metabolites 2020; 10(11): 450.
[http://dx.doi.org/10.3390/metabo10110450] [PMID: 33171879]
[10]
Sędzikowska A, Szablewski L. Insulin and insulin resistance in Alzheimer’s disease. Int J Mol Sci 2021; 22(18): 9987.
[http://dx.doi.org/10.3390/ijms22189987] [PMID: 34576151]
[11]
Onaolapo OJ, Onaolapo AY. Melatonin and major neurocognitive disorders: Beyond the management of sleep and circadian rhythm dysfunction. Sleep Hypn 2018; 21(1): 73-96.
[http://dx.doi.org/10.5350/Sleep.Hypn.2019.21.0175]
[12]
Uddin MS, Kabir MT, Rahman MS, et al. Revisiting the amyloid cascade hypothesis: from anti-aβ therapeutics to auspicious new ways for Alzheimer’s disease. Int J Mol Sci 2020; 21(16): 5858.
[http://dx.doi.org/10.3390/ijms21165858] [PMID: 32824102]
[13]
Harrison JR, Owen MJ. Alzheimer’s disease: The amyloid hypothesis on trial. Br J Psychiatry 2016; 208(1): 1-3.
[http://dx.doi.org/10.1192/bjp.bp.115.167569] [PMID: 26729836]
[14]
Makin S. The amyloid hypothesis on trial. Nature 2018; 559(7715): S4-7.
[http://dx.doi.org/10.1038/d41586-018-05719-4] [PMID: 30046080]
[15]
Panza F, Lozupone M, Logroscino G, Imbimbo BP. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol 2019; 15(2): 73-88.
[http://dx.doi.org/10.1038/s41582-018-0116-6] [PMID: 30610216]
[16]
Chen K, Zhuang Z, Shao C, et al. Roles of cardiometabolic factors in mediating the causal effect of type 2 diabetes on cardiovascular diseases: a two-step, two-sample multivariable mendelian randomization study. Front Cardiovasc Med 2022; 9: 813208.
[http://dx.doi.org/10.3389/fcvm.2022.813208] [PMID: 35282373]
[17]
Hu Y, Zhou Y, Yang Y, et al. Metformin protects against diabetes-induced cognitive dysfunction by inhibiting mitochondrial fission protein DRP1. Front Pharmacol 2022; 13: 832707.
[http://dx.doi.org/10.3389/fphar.2022.832707] [PMID: 35392573]
[18]
Jayaraj RL, Azimullah S, Beiram R. Diabetes as a risk factor for Alzheimer’s disease in the Middle East and its shared pathological mediators. Saudi J Biol Sci 2020; 27(2): 736-50.
[http://dx.doi.org/10.1016/j.sjbs.2019.12.028] [PMID: 32210695]
[19]
Kubis-Kubiak A, Wiatrak B, Piwowar A. The impact of high glucose or insulin exposure on S100B protein levels, oxidative and nitrosative stress and DNA damage in neuron-like cells. Int J Mol Sci 2021; 22(11): 5526.
[http://dx.doi.org/10.3390/ijms22115526] [PMID: 34073816]
[20]
Sun Y, Ma C, Sun H, et al. Metabolism: a novel shared link between diabetes mellitus and Alzheimer’s disease. J Diabetes Res 2020; 2020: 1-12.
[http://dx.doi.org/10.1155/2020/4981814] [PMID: 32083135]
[21]
Gamba P, Staurenghi E, Testa G, Giannelli S, Sottero B, Leonarduzzi G. A crosstalk between brain cholesterol oxidation and glucose metabolism in Alzheimer’s disease. Front Neurosci 2019; 13: 556.
[http://dx.doi.org/10.3389/fnins.2019.00556] [PMID: 31213973]
[22]
Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine 2019; 14: 5541-54.
[http://dx.doi.org/10.2147/IJN.S200490] [PMID: 31410002]
[23]
Goedert M. Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aβ tau, and α-synuclein. Science 2015; 349(6248): 1255555.
[http://dx.doi.org/10.1126/science.1255555] [PMID: 26250687]
[24]
Murphy MP, LeVine H III. Alzheimer’s disease and the amyloid-beta peptide. J Alzheimers Dis 2010; 19(1): 311-23.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[25]
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8(6): 595-608.
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[26]
Kametani F, Hasegawa M. Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer’s disease. Front Neurosci 2018; 12: 25.
[http://dx.doi.org/10.3389/fnins.2018.00025] [PMID: 29440986]
[27]
Maccioni RB, Farías G, Morales I, Navarrete L. The revitalized tau hypothesis on Alzheimer’s disease. Arch Med Res 2010; 41(3): 226-31.
[http://dx.doi.org/10.1016/j.arcmed.2010.03.007] [PMID: 20682182]
[28]
Muralidar S, Ambi SV, Sekaran S, Thirumalai D, Palaniappan B. Role of tau protein in Alzheimer’s disease: The prime pathological player. Int J Biol Macromol 2020; 163: 1599-617.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.07.327] [PMID: 32784025]
[29]
Xia Y, Prokop S, Giasson BI. “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol Neurodegener 2021; 16(1): 37.
[http://dx.doi.org/10.1186/s13024-021-00460-5] [PMID: 34090488]
[30]
Brier MR, Gordon B, Friedrichsen K, et al. Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med 2016; 8(338): 338ra66.
[http://dx.doi.org/10.1126/scitranslmed.aaf2362] [PMID: 27169802]
[31]
Barron MR, Gartlon J, Dawson LA, Atkinson PJ, Pardon MC. Increasing tau 4r tau levels exacerbates hippocampal tau hyperphosphorylation in the htau model of tauopathy but also tau dephosphorylation following acute systemic inflammation. Front Immunol 2020; 11: 293.
[http://dx.doi.org/10.3389/fimmu.2020.00293] [PMID: 32194553]
[32]
Johnson KA, Schultz A, Betensky RA, et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol 2016; 79(1): 110-9.
[http://dx.doi.org/10.1002/ana.24546] [PMID: 26505746]
[33]
Gong CX, Iqbal K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem 2008; 15(23): 2321-8.
[http://dx.doi.org/10.2174/092986708785909111] [PMID: 18855662]
[34]
Irwin DJ. Tauopathies as clinicopathological entities. Parkinsonism Relat Disord 2016; 22(S1): S29-33.
[http://dx.doi.org/10.1016/j.parkreldis.2015.09.020]
[35]
Jiao YN, Zhang JS, Qiao WJ, et al. Kai-xin-san inhibits tau pathology and neuronal apoptosis in aged SAMP8 mice. Mol Neurobiol 2022; 59(5): 3294-309.
[http://dx.doi.org/10.1007/s12035-021-02626-0] [PMID: 35303280]
[36]
Blass JP, Sheu RKF, Gibson G. Inherent abnormalities in energy metabolism in Alzheimer disease. Interaction with cerebrovascular compromise. Ann N Y Acad Sci 2000; 903(1 VASCULAR FACT): 204-21.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06370.x] [PMID: 10818509]
[37]
Ardanaz CG, Ramírez MJ, Solas M. Brain metabolic alterations in Alzheimer’s disease. Int J Mol Sci 2022; 23(7): 3785.
[http://dx.doi.org/10.3390/ijms23073785] [PMID: 35409145]
[38]
Yin F, Sancheti H, Patil I, Cadenas E. Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radic Biol Med 2016; 100: 108-22.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.200] [PMID: 27154981]
[39]
Cox S, Ed. ENERGY Metabolism. Caballero B., Ed. Encyclopedia of Human Nutrition. (2nd ed.). Elsevier 2005; pp. 106-14.
[http://dx.doi.org/10.1016/B0-12-226694-3/00103-4]
[40]
Blanco A, Blanco G. Metabolism. Medical Biochemistry. Academic Press 2017; pp. 275-81.
[http://dx.doi.org/10.1016/B978-0-12-803550-4.00013-6]
[41]
Roberts SB, Rosenberg I. Nutrition and aging: changes in the regulation of energy metabolism with aging. Physiol Rev 2006; 86(2): 651-67.
[http://dx.doi.org/10.1152/physrev.00019.2005] [PMID: 16601270]
[42]
Mason EF, Rathmell JC. Cell metabolism: An essential link between cell growth and apoptosis. Biochim Biophys Acta Mol Cell Res 2011; 1813(4): 645-54.
[http://dx.doi.org/10.1016/j.bbamcr.2010.08.011] [PMID: 20816705]
[43]
Green DR, Galluzzi L, Kroemer G. Metabolic control of cell death. Science 2014; 345(6203): 1250256.
[http://dx.doi.org/10.1126/science.1250256] [PMID: 25237106]
[44]
Burgeiro A, Cerqueira M, Varela-Rodríguez B, et al. Glucose and lipid dysmetabolism in a rat model of prediabetes induced by a high-sucrose diet. Nutrients 2017; 9(6): 638.
[http://dx.doi.org/10.3390/nu9060638] [PMID: 28635632]
[45]
Onaolapo AY, Adebisi EO, Adeleye AE, Olofinnade AT, Onaolapo OJ. Dietary melatonin protects against behavioural, metabolic, oxidative, and organ morphological changes in mice that are fed high-fat, high-sugar diet. Endocr Metab Immune Disord Drug Targets 2020; 20(4): 570-83.
[http://dx.doi.org/10.2174/1871530319666191009161228] [PMID: 32138638]
[46]
Onaolapo OJ, Adeyemi OI, Amujoyegbe OJ, Fasola EA, Olofinnade AT, Onaolapo AY. High dietary fat modulates neurobehavioural effect of lopinavir/ritonavir in mice. Curr Pharm Biotechnol 2020; 21(2): 158-68.
[http://dx.doi.org/10.2174/1389201020666191011144930] [PMID: 31612827]
[47]
Olofinnade AT, Alawode A, Onaolapo AY, Onaolapo OJ. Lepidium meyenii Supplemented diet modulates neurobehavioral and biochemical parameters in mice fed high-fat high-sugar diet. Endocr Metab Immune Disord Drug Targets 2021; 21(7): 1333-43.
[http://dx.doi.org/10.2174/1871530320666200821155005] [PMID: 32955007]
[48]
Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 2013; 36(10): 587-97.
[http://dx.doi.org/10.1016/j.tins.2013.07.001] [PMID: 23968694]
[49]
Lundqvist MH, Almby K, Abrahamsson N, Eriksson JW. Is the brain a key player in glucose regulation and development of type 2 diabetes? Front Physiol 2019; 10: 457.
[http://dx.doi.org/10.3389/fphys.2019.00457] [PMID: 31133864]
[50]
Onaolapo AY, Onaolapo OJ. Peripheral and central glutamate dyshomeostasis in neurodegenerative disorders. Curr Neuropharmacol 2021; 19(7): 1069-89.
[http://dx.doi.org/10.2174/1570159X18666201015161919] [PMID: 33059576]
[51]
Watts ME, Pocock R, Claudianos C. Brain energy and oxygen metabolism: emerging role in normal function and disease. Front Mol Neurosci 2018; 11: 216.
[http://dx.doi.org/10.3389/fnmol.2018.00216] [PMID: 29988368]
[52]
Roh E, Song DK, Kim MS. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism. Exp Mol Med 2016; 48(3): e216.
[http://dx.doi.org/10.1038/emm.2016.4] [PMID: 26964832]
[53]
Ondaro J, Hernandez-Eguiazu H, Garciandia-Arcelus M, et al. Defects of nutrient signaling and autophagy in neurodegeneration. Front Cell Dev Biol 2022; 10: 836196.
[http://dx.doi.org/10.3389/fcell.2022.836196] [PMID: 35419363]
[54]
Ivanov A, Zilberter Y. Critical state of energy metabolism in brain slices: the principal role of oxygen delivery and energy substrates in shaping neuronal activity. Front Neuroenergetics 2011; 3: 9.
[http://dx.doi.org/10.3389/fnene.2011.00009] [PMID: 22232599]
[55]
Rangaraju V, Lewis TL Jr, Hirabayashi Y, et al. Pleiotropic mitochondria: the influence of mitochondria on neuronal development and disease. J Neurosci 2019; 39(42): 8200-8.
[http://dx.doi.org/10.1523/JNEUROSCI.1157-19.2019] [PMID: 31619488]
[56]
Vergara RC, Jaramillo-Riveri S, Luarte A, et al. The energy homeostasis principle: neuronal energy regulation drives local network dynamics generating behavior. Front Comput Neurosci 2019; 13: 49.
[http://dx.doi.org/10.3389/fncom.2019.00049] [PMID: 31396067]
[57]
Morton GJ, Meek TH, Schwartz MW. Neurobiology of food intake in health and disease. Nat Rev Neurosci 2014; 15(6): 367-78.
[http://dx.doi.org/10.1038/nrn3745] [PMID: 24840801]
[58]
Sandoval D, Cota D, Seeley RJ. The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation. Annu Rev Physiol 2008; 70(1): 513-35.
[http://dx.doi.org/10.1146/annurev.physiol.70.120806.095256] [PMID: 17988209]
[59]
Kleinridders A, Könner AC, Brüning JC. CNS-targets in control of energy and glucose homeostasis. Curr Opin Pharmacol 2009; 9(6): 794-804.
[http://dx.doi.org/10.1016/j.coph.2009.10.006] [PMID: 19884043]
[60]
Gutierrez-Aguilar R, Grayson BE, Kim DH, et al. CNS GNPDA2 does not control appetite, but regulates glucose homeostasis. Front Nutr 2021; 8: 787470.
[http://dx.doi.org/10.3389/fnut.2021.787470] [PMID: 34912841]
[61]
Nogueiras R. Mechanisms in endocrinology: The gut–brain axis: regulating energy balance independent of food intake. Eur J Endocrinol 2021; 185(3): R75-91.
[http://dx.doi.org/10.1530/EJE-21-0277] [PMID: 34260412]
[62]
Schwartz MW, Porte D Jr. Diabetes, obesity, and the brain. Science 2005; 307(5708): 375-9.
[http://dx.doi.org/10.1126/science.1104344] [PMID: 15662002]
[63]
Cota D, Proulx K, Seeley RJ. The role of CNS fuel sensing in energy and glucose regulation. Gastroenterology 2007; 132(6): 2158-68.
[http://dx.doi.org/10.1053/j.gastro.2007.03.049] [PMID: 17498509]
[64]
Nakrani MN, Wineland RH, Anjum F. Physiology, Glucose Metabolism. StatPearls. Treasure Island, FL: StatPearls Publishing 2022. https://www.ncbi.nlm.nih.gov/books/NBK560599/Internet
[65]
Grayson BE, Seeley RJ, Sandoval DA. Wired on sugar: the role of the CNS in the regulation of glucose homeostasis. Nat Rev Neurosci 2013; 14(1): 24-37.
[http://dx.doi.org/10.1038/nrn3409] [PMID: 23232606]
[66]
van Hall G, Stømstad M, Rasmussen P, et al. Blood lactate is an important energy source for the human brain. J Cereb Blood Flow Metab 2009; 29(6): 1121-9.
[http://dx.doi.org/10.1038/jcbfm.2009.35] [PMID: 19337275]
[67]
Hashimoto T, Tsukamoto H, Ando S, Ogoh S. Effect of exercise on brain health: The potential role of lactate as a myokine. Metabolites 2021; 11(12): 813.
[http://dx.doi.org/10.3390/metabo11120813] [PMID: 34940571]
[68]
Kao YC, Ho PC, Tu YK, Jou IM, Tsai KJ. Lipids and Alzheimer’s disease. Int J Mol Sci 2020; 21(4): 1505.
[http://dx.doi.org/10.3390/ijms21041505] [PMID: 32098382]
[69]
Bruce KD, Zsombok A, Eckel RH. Lipid processing in the brain: A key regulator of systemic metabolism. Front Endocrinol 2017; 8: 60.
[http://dx.doi.org/10.3389/fendo.2017.00060] [PMID: 28421037]
[70]
Hamilton JA, Hillard CJ, Spector AA, Watkins PA. Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disorders. J Mol Neurosci 2007; 33(1): 2-11.
[http://dx.doi.org/10.1007/s12031-007-0060-1] [PMID: 17901539]
[71]
Naudí A, Cabré R, Jové M, et al. Lipidomics of human brain aging and Alzheimer’s disease pathology. Int Rev Neurobiol 2015; 122: 133-89.
[http://dx.doi.org/10.1016/bs.irn.2015.05.008] [PMID: 26358893]
[72]
Jové M, Pradas I, Dominguez-Gonzalez M, Ferrer I, Pamplona R. Lipids and lipoxidation in human brain aging. Mitochondrial ATP-synthase as a key lipoxidation target. Redox Biol 2019; 23: 101082.
[http://dx.doi.org/10.1016/j.redox.2018.101082] [PMID: 30635167]
[73]
Barber CN, Raben DM. Lipid metabolism crosstalk in the brain: Glia and neurons. Front Cell Neurosci 2019; 13: 212.
[http://dx.doi.org/10.3389/fncel.2019.00212] [PMID: 31164804]
[74]
Romano A, Koczwara JB, Gallelli CA, et al. Fats for thoughts: An update on brain fatty acid metabolism. Int J Biochem Cell Biol 2017; 84: 40-5.
[http://dx.doi.org/10.1016/j.biocel.2016.12.015] [PMID: 28065757]
[75]
Tracey TJ, Steyn FJ, Wolvetang EJ, Ngo ST. Neuronal lipid metabolism: multiple pathways driving functional outcomes in health and disease. Front Mol Neurosci 2018; 11: 10.
[http://dx.doi.org/10.3389/fnmol.2018.00010] [PMID: 29410613]
[76]
Rapoport SI, Chang MCJ, Spector AA. Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J Lipid Res 2001; 42(5): 678-85.
[http://dx.doi.org/10.1016/S0022-2275(20)31629-1] [PMID: 11352974]
[77]
Smith QR, Nagura H. Fatty acid uptake and incorporation in brain: studies with the perfusion model. J Mol Neurosci 2001; 16(2-3): 167-72.
[http://dx.doi.org/10.1385/JMN:16:2-3:167] [PMID: 11478371]
[78]
Murphy EJ, Owada Y, Kitanaka N, Kondo H, Glatz JFC. Brain arachidonic acid incorporation is decreased in heart fatty acid binding protein gene-ablated mice. Biochemistry 2005; 44(16): 6350-60.
[http://dx.doi.org/10.1021/bi047292r] [PMID: 15835924]
[79]
Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE. Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing. Am J Physiol Regul Integr Comp Physiol 2009; 297(3): R655-64.
[http://dx.doi.org/10.1152/ajpregu.00223.2009] [PMID: 19535676]
[80]
Mitchell RW, Hatch GM. Fatty acid transport into the brain: Of fatty acid fables and lipid tails. Prostaglandins Leukot Essent Fatty Acids 2011; 85(5): 293-302.
[http://dx.doi.org/10.1016/j.plefa.2011.04.007] [PMID: 21816594]
[81]
Le Foll C, Dunn-Meynell AA, Miziorko HM, Levin BE. Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids. Diabetes 2014; 63(4): 1259-69.
[http://dx.doi.org/10.2337/db13-1090] [PMID: 24379353]
[82]
Le Foll C, Dunn-Meynell AA, Miziorko HM, Levin BE. Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats. Am J Physiol Regul Integr Comp Physiol 2015; 308(10): R872-8.
[http://dx.doi.org/10.1152/ajpregu.00015.2015] [PMID: 25786485]
[83]
Bouyakdan K, Taïb B, Budry L, et al. A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes. J Neurochem 2015; 133(2): 253-65.
[http://dx.doi.org/10.1111/jnc.13035] [PMID: 25598214]
[84]
Ebrahimi M, Yamamoto Y, Sharifi K, et al. Astrocyte-expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons. Glia 2016; 64(1): 48-62.
[http://dx.doi.org/10.1002/glia.22902] [PMID: 26296243]
[85]
Zhang J, Liu Q. Cholesterol metabolism and homeostasis in the brain. Protein Cell 2015; 6(4): 254-64.
[http://dx.doi.org/10.1007/s13238-014-0131-3] [PMID: 25682154]
[86]
Söderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human brain during aging. J Neurochem 1990; 54(2): 415-23.
[http://dx.doi.org/10.1111/j.1471-4159.1990.tb01889.x] [PMID: 2299344]
[87]
Svennerholm L, Boström K, Jungbjer B, Olsson L. Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J Neurochem 1994; 63(5): 1802-11.
[http://dx.doi.org/10.1046/j.1471-4159.1994.63051802.x] [PMID: 7931336]
[88]
Linetti A, Fratangeli A, Taverna E, et al. Cholesterol reduction impairs exocytosis of synaptic vesicles. J Cell Sci 2010; 123(4): 595-605.
[http://dx.doi.org/10.1242/jcs.060681] [PMID: 20103534]
[89]
Liu Q, Trotter J, Zhang J, et al. Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J Neurosci 2010; 30(50): 17068-78.
[http://dx.doi.org/10.1523/JNEUROSCI.4067-10.2010] [PMID: 21159977]
[90]
Igarashi M, Ma K, Gao F, Kim HW, Rapoport SI, Rao JS. Disturbed choline plasmalogen and phospholipid fatty acid concentrations in Alzheimer’s disease prefrontal cortex. J Alzheimers Dis 2011; 24(3): 507-17.
[http://dx.doi.org/10.3233/JAD-2011-101608] [PMID: 21297269]
[91]
Emre C, Do KV, Jun B, et al. Age-related changes in brain phospholipids and bioactive lipids in the APP knock-in mouse model of Alzheimer’s disease. Acta Neuropathol Commun 2021; 9(1): 116.
[http://dx.doi.org/10.1186/s40478-021-01216-4] [PMID: 34187579]
[92]
Pettegrew JW, Panchalingam K, Hamilton RL, McClure RJ. Brain membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res 2001; 26(7): 771-82.
[http://dx.doi.org/10.1023/A:1011603916962] [PMID: 11565608]
[93]
Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR. Regional membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res 1998; 23(1): 81-8.
[http://dx.doi.org/10.1023/A:1022457605436] [PMID: 9482271]
[94]
Cunnane SC, Schneider JA, Tangney C, et al. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 2012; 29(3): 691-7.
[http://dx.doi.org/10.3233/JAD-2012-110629] [PMID: 22466064]
[95]
Astarita G, Jung KM, Berchtold NC, et al. Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer’s disease. PLoS One 2010; 5(9): e12538.
[http://dx.doi.org/10.1371/journal.pone.0012538] [PMID: 20838618]
[96]
Ooi KLM, Vacy K, Boon WC. Fatty acids and beyond: Age and Alzheimer’s disease related changes in lipids reveal the neuro-nutraceutical potential of lipids in cognition. Neurochem Int 2021; 149: 105143.
[http://dx.doi.org/10.1016/j.neuint.2021.105143] [PMID: 34311029]
[97]
Onaolapo AY, Onaolapo OJ. Circadian dysrhythmia-linked diabetes mellitus: Examining melatonin’s roles in prophylaxis and management. World J Diabetes 2018; 9(7): 99-114.
[http://dx.doi.org/10.4239/wjd.v9.i7.99] [PMID: 30079146]
[98]
Onaolapo AY, Onaolapo OJ. African Plants with Antidiabetic Potentials: Beyond Glycaemic Control to Central Nervous System Benefits. Curr Diabetes Rev 2020; 16(5): 419-37.
[http://dx.doi.org/10.2174/1573399815666191106104941] [PMID: 31702529]
[99]
Onaolapo AY, Onaolapo OJ. Nutraceuticals and diet-based phytochemicals in type 2 diabetes mellitus: From whole food to components with defined roles and mechanisms. Curr Diabetes Rev 2019; 16(1): 12-25.
[http://dx.doi.org/10.2174/1573399814666181031103930] [PMID: 30378500]
[100]
Maida CD, Daidone M, Pacinella G, Norrito RL, Pinto A, Tuttolomondo A. Diabetes and ischemic stroke: An old and new relationship an overview of the close interaction between these diseases. Int J Mol Sci 2022; 23(4): 2397.
[http://dx.doi.org/10.3390/ijms23042397] [PMID: 35216512]
[101]
Pinto RS, Minanni CA, de Araújo Lira AL, Passarelli M. Advanced glycation end products: A sweet flavor that embitters cardiovascular disease. Int J Mol Sci 2022; 23(5): 2404.
[http://dx.doi.org/10.3390/ijms23052404] [PMID: 35269546]
[102]
Biesenbach G. Fettstoffwechselstörungen bei diabetes mellitus. Wien Med Wochenschr Suppl 1989; 105: 9-17.
[PMID: 2694631]
[103]
Savage DB, Petersen KF, Shulman GI. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 2007; 87(2): 507-20.
[http://dx.doi.org/10.1152/physrev.00024.2006] [PMID: 17429039]
[104]
Vergès BL. Dyslipidaemia in diabetes mellitus. Review of the main lipoprotein abnormalities and their consequences on the development of atherogenesis. Diabetes Metab 1999; 25(S3): 32-40.
[PMID: 10421991]
[105]
Albai O, Roman D, Frandes M. Hypertriglyceridemia, an important and independent risk factor for acute pancreatitis in patients with type 2 diabetes mellitus. Ther Clin Risk Manag 2017; 13: 515-22.
[http://dx.doi.org/10.2147/TCRM.S134560] [PMID: 28450786]
[106]
Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009; 53(5): S35-42.
[http://dx.doi.org/10.1016/j.jacc.2008.09.055] [PMID: 19179216]
[107]
Mather KJ, Bebu I, Baker C, et al. Prevalence of microvascular and macrovascular disease in the glycemia reduction approaches in diabetes - A comparative effectiveness (GRADE) study cohort. Diabetes Res Clin Pract 2020; 165: 108235.
[http://dx.doi.org/10.1016/j.diabres.2020.108235] [PMID: 32450102]
[108]
Sinclair SH, Schwartz SS. Diabetic retinopathy–an underdiagnosed and undertreated inflammatory, neuro-vascular complication of diabetes. Front Endocrinol 2019; 10: 843.
[http://dx.doi.org/10.3389/fendo.2019.00843] [PMID: 31920963]
[109]
Wrighten SA, Piroli GG, Grillo CA, Reagan LP. A look inside the diabetic brain: Contributors to diabetes-induced brain aging. Biochim Biophys Acta Mol Basis Dis 2009; 1792(5): 444-53.
[http://dx.doi.org/10.1016/j.bbadis.2008.10.013] [PMID: 19022375]
[110]
Bharadwaj P, Wijesekara N, Liyanapathirana M, et al. The link between type 2 diabetes and neurodegeneration: Roles for amyloid-β amylin, and tau proteins. J Alzheimers Dis 2017; 59(2): 421-32.
[http://dx.doi.org/10.3233/JAD-161192] [PMID: 28269785]
[111]
Olofinnade AT, Onaolapo AY, Onaolapo OJ, et al. Corylus avellana L. modulates neurobehaviour and brain chemistry following high-fat diet. Front Biosci 2021; 26(3): 537-51.
[http://dx.doi.org/10.2741/4906] [PMID: 33049682]
[112]
Hamed SA. Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications. Expert Rev Clin Pharmacol 2017; 10(4): 409-28.
[http://dx.doi.org/10.1080/17512433.2017.1293521] [PMID: 28276776]
[113]
McEwen BS, Reagan LP. Glucose transporter expression in the central nervous system: relationship to synaptic function. Eur J Pharmacol 2004; 490(1-3): 13-24.
[http://dx.doi.org/10.1016/j.ejphar.2004.02.041] [PMID: 15094070]
[114]
Koepsell H. Glucose transporters in brain in health and disease. Pflugers Arch 2020; 472(9): 1299-343.
[http://dx.doi.org/10.1007/s00424-020-02441-x] [PMID: 32789766]
[115]
Craven RJ, Frazier HN, Thibault O. Dependence of glucose transport on autophagy and GAPDH activity. Brain Res 2022; 1776: 147747.
[http://dx.doi.org/10.1016/j.brainres.2021.147747] [PMID: 34864044]
[116]
Saravia FE, Revsin Y, Gonzalez Deniselle MC, et al. Increased astrocyte reactivity in the hippocampus of murine models of type 1 diabetes: the nonobese diabetic (NOD) and streptozotocin-treated mice. Brain Res 2002; 957(2): 345-53.
[http://dx.doi.org/10.1016/S0006-8993(02)03675-2] [PMID: 12445977]
[117]
Coleman E, Judd R, Hoe L, Dennis J, Posner P. Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS. Glia 2004; 48(2): 166-78.
[http://dx.doi.org/10.1002/glia.20068] [PMID: 15378652]
[118]
Zelena D, Filaretova L, Mergl Z, Barna I, Tóth ZE, Makara GB. Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats. Am J Physiol Endocrinol Metab 2006; 290(2): E243-50.
[http://dx.doi.org/10.1152/ajpendo.00118.2005] [PMID: 16144820]
[119]
Beauquis J, Homo-Delarche F, Revsin Y, De Nicola AF, Saravia F. Brain alterations in autoimmune and pharmacological models of diabetes mellitus: focus on hypothalamic-pituitary-adrenocortical axis disturbances. Neuroimmunomodulation 2008; 15(1): 61-7.
[http://dx.doi.org/10.1159/000135625] [PMID: 18667801]
[120]
Beauquis J, Saravia F, Coulaud J, et al. Prominently decreased hippocampal neurogenesis in a spontaneous model of type 1 diabetes, the nonobese diabetic mouse. Exp Neurol 2008; 210(2): 359-67.
[http://dx.doi.org/10.1016/j.expneurol.2007.11.009] [PMID: 18190910]
[121]
Guo J, Yu C, Li H, et al. Impaired neural stem/progenitor cell proliferation in streptozotocin-induced and spontaneous diabetic mice. Neurosci Res 2010; 68(4): 329-36.
[http://dx.doi.org/10.1016/j.neures.2010.08.012] [PMID: 20832431]
[122]
Rizvi SM, Shaikh S, Waseem SM, et al. Role of anti-diabetic drugs as therapeutic agents in Alzheimer’s disease. EXCLI J 2015; 14: 684-96.
[http://dx.doi.org/10.17179/excli2015-252] [PMID: 27152105]
[123]
Reaven GM, Thompson LW, Nahum D, Haskins E. Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care 1990; 13(1): 16-21.
[http://dx.doi.org/10.2337/diacare.13.1.16] [PMID: 2298111]
[124]
Cukierman-Yaffe T, Gerstein HC, Williamson JD, et al. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care 2009; 32(2): 221-6.
[http://dx.doi.org/10.2337/dc08-1153] [PMID: 19171735]
[125]
Thomas VS, Darvesh S, MacKnight C, Rockwood K. Estimating the prevalence of dementia in elderly people: a comparison of the Canadian Study of Health and Aging and National Population Health Survey approaches. Int Psychogeriatr 2001; 13(S1) (Suppl. 1): 169-75.
[http://dx.doi.org/10.1017/S1041610202008116] [PMID: 11892964]
[126]
S Roriz-Filho J, Sá-Roriz TM, Rosset I, et al. (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta 2009; 1792(5): 432-43.
[http://dx.doi.org/10.1016/j.bbadis.2008.12.003] [PMID: 19135149]
[127]
Bordier L, Doucet J, Boudet J, Bauduceau B. Update on cognitive decline and dementia in elderly patients with diabetes. Diabetes Metab 2014; 40(5): 331-7.
[http://dx.doi.org/10.1016/j.diabet.2014.02.002] [PMID: 24703603]
[128]
Ott A, Stolk RP, van Harskamp F, Pols HAP, Hofman A, Breteler MMB. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 1999; 53(9): 1937-42.
[http://dx.doi.org/10.1212/WNL.53.9.1937] [PMID: 10599761]
[129]
Seaquist ER. The final frontier: how does diabetes affect the brain? Diabetes 2010; 59(1): 4-5.
[http://dx.doi.org/10.2337/db09-1600] [PMID: 20040482]
[130]
Reijmer YD, van den Berg E, Ruis C, Jaap Kappelle L, Biessels GJ. Cognitive dysfunction in patients with type 2 diabetes. Diabetes Metab Res Rev 2010; 26(7): 507-19.
[http://dx.doi.org/10.1002/dmrr.1112] [PMID: 20799243]
[131]
Williamson R, McNeilly A, Sutherland C. Insulin resistance in the brain: An old-age or new-age problem? Biochem Pharmacol 2012; 84(6): 737-45.
[http://dx.doi.org/10.1016/j.bcp.2012.05.007] [PMID: 22634336]
[132]
Steculorum SM, Solas M, Brüning JC. The paradox of neuronal insulin action and resistance in the development of aging‐associated diseases. Alzheimers Dement 2014; 10(1S) (Suppl.): S3-S11.
[http://dx.doi.org/10.1016/j.jalz.2013.12.008] [PMID: 24529522]
[133]
Zhou Y, Zhao Y, Xie H, Wang Y, Liu L, Yan X. Alteration in amyloid β42, phosphorylated tau protein, interleukin 6, and acetylcholine during diabetes-accelerated memory dysfunction in diabetic rats: correlation of amyloid β42 with changes in glucose metabolism. Behav Brain Funct 2015; 11(1): 24.
[http://dx.doi.org/10.1186/s12993-015-0069-5] [PMID: 26271247]
[134]
Zhang Y, Huang N, Yan F, et al. Diabetes mellitus and Alzheimer’s disease: GSK-3β as a potential link. Behav Brain Res 2018; 339: 57-65.
[http://dx.doi.org/10.1016/j.bbr.2017.11.015] [PMID: 29158110]
[135]
Kawamura T, Umemura T, Hotta N. Cognitive impairment in diabetic patients: Can diabetic control prevent cognitive decline? J Diabetes Investig 2012; 3(5): 413-23.
[http://dx.doi.org/10.1111/j.2040-1124.2012.00234.x] [PMID: 24843599]
[136]
Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol 2009; 66(3): 300-5.
[http://dx.doi.org/10.1001/archneurol.2009.27] [PMID: 19273747]
[137]
Verdile G, Fuller SJ, Martins RN. The role of type 2 diabetes in neurodegeneration. Neurobiol Dis 2015; 84: 22-38.
[http://dx.doi.org/10.1016/j.nbd.2015.04.008] [PMID: 25926349]
[138]
Cui X, Abduljalil A, Manor BD, Peng CK, Novak V. Multi-scale glycemic variability: a link to gray matter atrophy and cognitive decline in type 2 diabetes. PLoS One 2014; 9(1): e86284.
[http://dx.doi.org/10.1371/journal.pone.0086284] [PMID: 24475100]
[139]
Zhao X, Han Q, Lv Y, Sun L, Gang X, Wang G. Biomarkers for cognitive decline in patients with diabetes mellitus: evidence from clinical studies. Oncotarget 2018; 9(7): 7710-26.
[http://dx.doi.org/10.18632/oncotarget.23284] [PMID: 29484146]
[140]
Sluiman AJ, McLachlan S, Forster RB, Strachan MWJ, Deary IJ, Price JF. Higher baseline inflammatory marker levels predict greater cognitive decline in older people with type 2 diabetes: year 10 follow-up of the Edinburgh type 2 diabetes study. Diabetologia 2022; 65(3): 467-76.
[http://dx.doi.org/10.1007/s00125-021-05634-w] [PMID: 34932135]
[141]
Wijesekara N, Ahrens R, Sabale M, et al. Amyloid‐β and islet amyloid pathologies link Alzheimer’s disease and type 2 diabetes in a transgenic model. FASEB J 2017; 31(12): 5409-18.
[http://dx.doi.org/10.1096/fj.201700431R] [PMID: 28808140]
[142]
Ma WX, Tang J, Lei ZW, et al. Potential biochemical mechanisms of brain injury in diabetes mellitus. Aging Dis 2020; 11(4): 978-87.
[http://dx.doi.org/10.14336/AD.2019.0910] [PMID: 32765958]
[143]
Cummings J, Ortiz A, Castellino J, Kinney J. Diabetes: Risk factor and translational therapeutic implications for Alzheimer’s disease. Eur J Neurosci 2022; 56(9): 5727-57. Epub ahead of print
[http://dx.doi.org/10.1111/ejn.15619] [PMID: 35128745]
[144]
Qiu W, Folstein M. Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer’s disease: review and hypothesis. Neurobiol Aging 2006; 27(2): 190-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.01.004] [PMID: 16399206]
[145]
Luchsinger JA. Adiposity, hyperinsulinemia, diabetes and Alzheimer’s disease. Eur J Pharmacol 2008; 585(1): 119-29.
[http://dx.doi.org/10.1016/j.ejphar.2008.02.048] [PMID: 18384771]
[146]
Schrijvers EMC, Witteman JCM, Sijbrands EJG, Hofman A, Koudstaal PJ, Breteler MMB. Insulin metabolism and the risk of Alzheimer disease: The rotterdam study. Neurology 2010; 75(22): 1982-7.
[http://dx.doi.org/10.1212/WNL.0b013e3181ffe4f6] [PMID: 21115952]
[147]
Matsuzaki T, Sasaki K, Tanizaki Y, et al. Insulin resistance is associated with the pathology of Alzheimer disease: The hisayama study. Neurology 2010; 75(9): 764-70.
[http://dx.doi.org/10.1212/WNL.0b013e3181eee25f] [PMID: 20739649]
[148]
de la Monte SM. Brain insulin resistance and deficiency as therapeutic targets in Alzheimer’s disease. Curr Alzheimer Res 2012; 9(1): 35-66.
[http://dx.doi.org/10.2174/156720512799015037] [PMID: 22329651]
[149]
O’Neill C, Kiely AP, Coakley MF, Manning S, Long-Smith CM. Insulin and IGF-1 signalling: longevity, protein homoeostasis and Alzheimer’s disease. Biochem Soc Trans 2012; 40(4): 721-7.
[http://dx.doi.org/10.1042/BST20120080] [PMID: 22817723]
[150]
Schiöth HB, Craft S, Brooks SJ, Frey WH II, Benedict C. Brain insulin signaling and Alzheimer’s disease: current evidence and future directions. Mol Neurobiol 2012; 46(1): 4-10.
[http://dx.doi.org/10.1007/s12035-011-8229-6] [PMID: 22205300]
[151]
Park S, Kim DS, Kang S, Moon NR. β-Amyloid-induced cognitive dysfunction impairs glucose homeostasis by increasing insulin resistance and decreasing β-cell mass in non-diabetic and diabetic rats. Metabolism 2013; 62(12): 1749-60.
[http://dx.doi.org/10.1016/j.metabol.2013.08.007] [PMID: 24050268]
[152]
Reinke C, Buchmann N, Fink A, Tegeler C, Demuth I, Doblhammer G. Diabetes duration and the risk of dementia: a cohort study based on German health claims data. Age Ageing 2022; 51(1): afab231.
[http://dx.doi.org/10.1093/ageing/afab231] [PMID: 34923587]
[153]
Yamagishi S, Nakamura K, Inoue H, Kikuchi S, Takeuchi M. Serum or cerebrospinal fluid levels of glyceraldehyde-derived advanced glycation end products (AGEs) may be a promising biomarker for early detection of Alzheimer’s disease. Med Hypotheses 2005; 64(6): 1205-7.
[http://dx.doi.org/10.1016/j.mehy.2005.01.016] [PMID: 15823718]
[154]
Jia X, Olson DJH, Ross ARS, et al. Structural and functional changes in human insulin induced by methylglyoxal. FASEB J 2006; 20(9): 1555-7.
[http://dx.doi.org/10.1096/fj.05-5478fje] [PMID: 16723378]
[155]
Alagiakrishnan K, Sankaralingam S, Ghosh M, Mereu L, Senior P. Antidiabetic drugs and their potential role in treating mild cognitive impairment and Alzheimer’s disease. Discov Med 2013; 16(90): 277-86.
[PMID: 24333407]
[156]
Ahmed AS, Elgharabawy RM,. AL-Najjar AH. Ameliorating effect of anti-Alzheimer’s drugs on the bidirectional association between type 2 diabetes mellitus and Alzheimer’s disease. Exp Biol Med (Maywood) 2017; 242(13): 1335-44.
[http://dx.doi.org/10.1177/1535370217711440] [PMID: 28534431]
[157]
Markowicz-Piasecka M, Sikora J, Szydłowska A, Skupień A, Mikiciuk-Olasik E, Huttunen KM. Metformin - a future therapy for neurodegenerative diseases: Theme: Drug discovery, development and delivery in Alzheimer's disease. Pharm Res 2017; 34(12): 2614-27.
[http://dx.doi.org/10.1007/s11095-017-2199-y]
[158]
Akimoto H, Negishi A, Oshima S, et al. Antidiabetic drugs for the risk of Alzheimer disease in patients with type 2 DM using FAERS. Am J Alzheimers Dis Other Demen 2020; 35.
[http://dx.doi.org/10.1177/1533317519899546] [PMID: 32162525]
[159]
Muñoz-Jiménez M, Zaarkti A, García-Arnés JA, García-Casares N. Antidiabetic drugs in Alzheimer’s disease and mild cognitive impairment: A systematic review. Dement Geriatr Cogn Disord 2020; 49(5): 423-34.
[http://dx.doi.org/10.1159/000510677] [PMID: 33080602]
[160]
Craft S, Raman R, Chow TW, et al. Safety, efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and Alzheimer disease dementia. JAMA Neurol 2020; 77(9): 1099-109.
[http://dx.doi.org/10.1001/jamaneurol.2020.1840] [PMID: 32568367]
[161]
Molnár G, Faragó N, Kocsis AK, et al. GABAergic neurogliaform cells represent local sources of insulin in the cerebral cortex. J Neurosci 2014; 34(4): 1133-7.
[http://dx.doi.org/10.1523/JNEUROSCI.4082-13.2014] [PMID: 24453306]
[162]
Freiherr J, Hallschmid M, Frey WH II, et al. Intranasal insulin as a treatment for Alzheimer’s disease: a review of basic research and clinical evidence. CNS Drugs 2013; 27(7): 505-14.
[http://dx.doi.org/10.1007/s40263-013-0076-8] [PMID: 23719722]
[163]
Reger MA, Watson GS, Frey WH II, et al. Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype. Neurobiol Aging 2006; 27(3): 451-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.03.016] [PMID: 15964100]
[164]
Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates -amyloid in early AD. Neurology 2008; 70(6): 440-8.
[http://dx.doi.org/10.1212/01.WNL.0000265401.62434.36] [PMID: 17942819]
[165]
Dhamoon MS, Noble JM, Craft S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 2009; 72(3): 292-4.
[http://dx.doi.org/10.1212/01.wnl.0000344246.91081.2c] [PMID: 19153380]
[166]
Ferreira IL, Resende R, Ferreiro E, Rego AC, Pereira CF. Multiple defects in energy metabolism in Alzheimer’s disease. Curr Drug Targets 2010; 11(10): 1193-206.
[http://dx.doi.org/10.2174/1389450111007011193] [PMID: 20840064]
[167]
Craft S, Baker LD, Montine TJ, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 2012; 69(1): 29-38.
[http://dx.doi.org/10.1001/archneurol.2011.233] [PMID: 21911655]
[168]
Claxton A, Baker LD, Wilkinson CW, et al. Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer’s disease. J Alzheimers Dis 2013; 35(4): 789-97.
[http://dx.doi.org/10.3233/JAD-122308] [PMID: 23507773]
[169]
Łabuzek K, Suchy D, Gabryel B, Bielecka A, Liber S, Okopień B. Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol Rep 2010; 62(5): 956-65.
[http://dx.doi.org/10.1016/S1734-1140(10)70357-1] [PMID: 21098880]
[170]
Gupta A, Bisht B, Dey CS. Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes. Neuropharmacology 2011; 60(6): 910-20.
[http://dx.doi.org/10.1016/j.neuropharm.2011.01.033] [PMID: 21277873]
[171]
Lu XY, Huang S, Chen QB, et al. Metformin Ameliorates A β Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease. Oxid Med Cell Longev 2020; 2020: 1-10.
[http://dx.doi.org/10.1155/2020/2315106] [PMID: 32377293]
[172]
Hampel H, Vassar R, De Strooper B, et al. The β-Secretase BACE1 in Alzheimer’s Disease. Biol Psychiatry 2021; 89(8): 745-56.
[http://dx.doi.org/10.1016/j.biopsych.2020.02.001] [PMID: 32223911]
[173]
Ou Z, Kong X, Sun X, et al. Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice. Brain Behav Immun 2018; 69: 351-63.
[http://dx.doi.org/10.1016/j.bbi.2017.12.009] [PMID: 29253574]
[174]
Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: from mechanisms of action to therapies. Cell Metab 2014; 20(6): 953-66.
[http://dx.doi.org/10.1016/j.cmet.2014.09.018] [PMID: 25456737]
[175]
Yang L, Jiang Y, Shi L, et al. AMPK: Potential Therapeutic Target for Alzheimer’s Disease. Curr Protein Pept Sci 2020; 21(1): 66-77.
[http://dx.doi.org/10.2174/1389203720666190819142746] [PMID: 31424367]
[176]
Chen F, Dong RR, Zhong KL, et al. Antidiabetic drugs restore abnormal transport of amyloid-β across the blood–brain barrier and memory impairment in db/db mice. Neuropharmacology 2016; 101: 123-36.
[http://dx.doi.org/10.1016/j.neuropharm.2015.07.023] [PMID: 26211973]
[177]
Mostafa DK, Ismail CA, Ghareeb DA. Differential metformin dose-dependent effects on cognition in rats: role of Akt. Psychopharmacology (Berl) 2016; 233(13): 2513-24.
[http://dx.doi.org/10.1007/s00213-016-4301-2] [PMID: 27113224]
[178]
Kickstein E, Krauss S, Thornhill P, et al. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci USA 2010; 107(50): 21830-5.
[http://dx.doi.org/10.1073/pnas.0912793107] [PMID: 21098287]
[179]
Li J, Deng J, Sheng W, Zuo Z. Metformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav 2012; 101(4): 564-74.
[http://dx.doi.org/10.1016/j.pbb.2012.03.002] [PMID: 22425595]
[180]
Chen Y, Zhao S, Fan Z, et al. Metformin attenuates plaque-associated tau pathology and reduces amyloid-β burden in APP/PS1 mice. Alzheimers Res Ther 2021; 13(1): 40.
[http://dx.doi.org/10.1186/s13195-020-00761-9] [PMID: 33563332]
[181]
Zhang J, Lin Y, Dai X, Fang W, Wu X, Chen X. Metformin treatment improves the spatial memory of aged mice in an APOE genotype–dependent manner. FASEB J 2019; 33(6): 7748-57.
[http://dx.doi.org/10.1096/fj.201802718R] [PMID: 30894020]
[182]
Kuhla A, Brichmann E, Rühlmann C, Thiele R, Meuth L, Vollmar B. Metformin therapy aggravates neurodegenerative processes in ApoE–/– mice. J Alzheimers Dis 2019; 68(4): 1415-27.
[http://dx.doi.org/10.3233/JAD-181017] [PMID: 30909226]
[183]
Huttunen KM, Leppänen J, Laine K, Vepsäläinen J, Rautio J. Convenient microwave-assisted synthesis of lipophilic sulfenamide prodrugs of metformin. Eur J Pharm Sci 2013; 49(4): 624-8.
[http://dx.doi.org/10.1016/j.ejps.2013.05.023] [PMID: 23732628]
[184]
Huttunen KM, Mannila A, Laine K, et al. The first bioreversible prodrug of metformin with improved lipophilicity and enhanced intestinal absorption. J Med Chem 2009; 52(14): 4142-8.
[http://dx.doi.org/10.1021/jm900274q] [PMID: 19522462]
[185]
Liao W, Xu J, Li B, Ruan Y, Li T, Liu J. Deciphering the roles of metformin in Alzheimer’s disease: A snapshot. Front Pharmacol 2022; 12: 728315.
[http://dx.doi.org/10.3389/fphar.2021.728315] [PMID: 35153733]
[186]
Kim J, Park JH, Shah K, Mitchell SJ, Cho K, Hoe HS. The anti-diabetic drug gliquidone modulates lipopolysaccharide-mediated microglial neuroinflammatory responses by inhibiting the NLRP3 inflammasome. Front Aging Neurosci 2021; 13: 754123.
[http://dx.doi.org/10.3389/fnagi.2021.754123] [PMID: 34776934]
[187]
Zullo AR, Duprey MS, Smith RJ, et al. Effects of dipeptidyl peptidase‐4 inhibitors and sulphonylureas on cognitive and physical function in nursing home residents. Diabetes Obes Metab 2022; 24(2): 247-56.
[http://dx.doi.org/10.1111/dom.14573] [PMID: 34647409]
[188]
Heneka MT, Klockgether T, Feinstein DL. Peroxisome proliferator-activated receptor-gamma ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. J Neurosci 2000; 20(18): 6862-7.
[http://dx.doi.org/10.1523/JNEUROSCI.20-18-06862.2000] [PMID: 10995830]
[189]
De Felice FG, Vieira MNN, Bomfim TR, et al. Protection of synapses against Alzheimer’s-linked toxins: Insulin signaling prevents the pathogenic binding of Aβ oligomers. Proc Natl Acad Sci USA 2009; 106(6): 1971-6.
[http://dx.doi.org/10.1073/pnas.0809158106] [PMID: 19188609]
[190]
Pathan AR, Viswanad B, Sonkusare SK, Ramarao P. Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life Sci 2006; 79(23): 2209-16.
[http://dx.doi.org/10.1016/j.lfs.2006.07.018] [PMID: 16904700]
[191]
Watson GS, Cholerton BA, Reger MA, et al. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry 2005; 13(11): 950-8.
[http://dx.doi.org/10.1176/appi.ajgp.13.11.950] [PMID: 16286438]
[192]
Risner ME, Saunders AM, Altman J F B, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J 2006; 6(4): 246-54.
[http://dx.doi.org/10.1038/sj.tpj.6500369] [PMID: 16446752]
[193]
Tzimopoulou S, Cunningham VJ, Nichols TE, et al. A multi-center randomized proof-of-concept clinical trial applying [¹⁸F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer’s disease. J Alzheimers Dis 2011; 22(4): 1241-56.
[http://dx.doi.org/10.3233/JAD-2010-100939] [PMID: 20930300]
[194]
Imfeld P, Bodmer M, Jick SS, Meier CR. Metformin, other antidiabetic drugs, and risk of Alzheimer’s disease: a population-based case-control study. J Am Geriatr Soc 2012; 60(5): 916-21.
[http://dx.doi.org/10.1111/j.1532-5415.2012.03916.x] [PMID: 22458300]
[195]
Hölscher C. The role of GLP-1 in neuronal activity and neurodegeneration. Vitam Horm 2010; 84: 331-54.
[http://dx.doi.org/10.1016/B978-0-12-381517-0.00013-8] [PMID: 21094907]
[196]
Bomfim TR, Forny-Germano L, Sathler LB, et al. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease–associated Aβ oligomers. J Clin Invest 2012; 122(4): 1339-53.
[http://dx.doi.org/10.1172/JCI57256] [PMID: 22476196]
[197]
Hunter K, Hölscher C. Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci 2012; 13(1): 33.
[http://dx.doi.org/10.1186/1471-2202-13-33] [PMID: 22443187]
[198]
McClean PL, Parthsarathy V, Faivre E, Hölscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J Neurosci 2011; 31(17): 6587-94.
[http://dx.doi.org/10.1523/JNEUROSCI.0529-11.2011] [PMID: 21525299]
[199]
Yang Y, Zhang J, Ma D, et al. Subcutaneous administration of liraglutide ameliorates Alzheimer-associated tau hyperphosphorylation in rats with type 2 diabetes. J Alzheimers Dis 2013; 37(3): 637-48.
[http://dx.doi.org/10.3233/JAD-130491] [PMID: 23948890]

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