Login Register Cart 0
Generic placeholder image

当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Review Article

AD中的炎症生物标志物：对诊断的意义

卷 17, 期 11, 2020

页: [962 - 971] 页: 10

弟呕挨: 10.2174/1567205017666201223152612

价格: $65

摘要

阿尔茨海默氏病是痴呆症最常见的形式。由于缺乏有效的干预措施，因此强调了对新干预措施进行早期准确诊断。但是，在诊断之前，明显的神经元丢失和神经病理损害会严重损害大脑。随着我们对神经炎症在阿尔茨海默氏病发病机理中的作用的了解不断增长，炎症性生物标志物在诊断中引起了越来越多的兴趣。这篇综述的重点是通过神经影像，脑脊液和外周血检测到的炎症生物标记物在诊断阿尔茨海默氏病中的用途，并提出了临床意义。这篇综述包括以下生物标志物：神经影像学，各种与转运蛋白（TSPO）结合的配体；脑脊液，在髓样细胞（sTREM2）,人软骨糖蛋白39（YKL-40）和单核细胞趋化蛋白1（MCP-1）上表达的可溶性触发受体，以及外周血中的各种生物标志物。尽管越来越多的证据表明这些炎症性生物标志物在诊断AD中具有潜在作用，但它们的使用仍存在局限性。但是，将这些生物标记物与常规诊断线索（例如基因型和淀粉样蛋白病理）结合使用，可以改善患者的分层和选择，以进行有针对性的早期干预。

关键词: 阿尔茨海默氏病，神经炎症，生物标志物，神经影像学，脑脊液，血浆，轻度认知障碍，小胶质细胞

« Previous Next »
[1]
Mayeux R, Stern Y. Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2(8)a006239
[http://dx.doi.org/10.1101/cshperspect.a006239] [PMID: 22908189]
[2]
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 2007; 3(3): 186-91.
[http://dx.doi.org/10.1016/j.jalz.2007.04.381] [PMID: 19595937]
[3]
Ziegler-Graham K, Brookmeyer R, Johnson E, Arrighi HM. Worldwide variation in the doubling time of Alzheimer’s disease incidence rates. Alzheimers Dement 2008; 4(5): 316-23.
[http://dx.doi.org/10.1016/j.jalz.2008.05.2479] [PMID: 18790458]
[4]
Amy R. .Borenstein. Survival and mortality in Alzheimer’s disease.(Ed: Borenstein AR) Alzheimer’s disease: life course perspectives on risk reduction. Elsevier 2016; pp. 89-94..
[5]
Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub 2013.
[http://dx.doi.org/10.1176/appi.books.9780890425596]
[6]
Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement 2018; 4: 575-90.
[http://dx.doi.org/10.1016/j.trci.2018.06.014] [PMID: 30406177]
[7]
London A, Cohen M, Schwartz M. Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair. Front Cell Neurosci 2013; 7(34): 34.
[http://dx.doi.org/10.3389/fncel.2013.00034] [PMID: 23596391]
[8]
Wyss-Coray T, Rogers J. Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med 2012; 2(1)a006346
[http://dx.doi.org/10.1101/cshperspect.a006346] [PMID: 22315714]
[9]
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 2015; 14(4): 388-405.
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[10]
Rubio-Perez JM, Morillas-Ruiz JMA. A review: inflammatory process in Alzheimer’s disease, role of cytokines. ScientificWorldJournal 2012; 2012756357
[http://dx.doi.org/10.1100/2012/756357] [PMID: 22566778]
[11]
Tuppo EE, Arias HR. The role of inflammation in Alzheimer’s disease. Int J Biochem Cell Biol 2005; 37(2): 289-305.
[http://dx.doi.org/10.1016/j.biocel.2004.07.009] [PMID: 15474976]
[12]
Walters A, Phillips E, Zheng R, Biju M, Kuruvilla T. Evidence for neuroinflammation in Alzheimer’s disease. Prog Neurol Psychiatry 2016; 20(5): 25-31.
[http://dx.doi.org/10.1002/pnp.444]
[13]
Mrak RE, Griffin WST. Common inflammatory mechanisms in Lewy body disease and Alzheimer disease. J Neuropathol Exp Neurol 2007; 66(8): 683-6.
[http://dx.doi.org/10.1097/nen.0b013e31812503e1] [PMID: 17882012]
[14]
Zhang B, Gaiteri C, Bodea L-G, et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer’s disease. Cell 2013; 153(3): 707-20.
[http://dx.doi.org/10.1016/j.cell.2013.03.030] [PMID: 23622250]
[15]
Griciuc A, Serrano-Pozo A, Parrado AR, et al. Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 2013; 78(4): 631-43.
[http://dx.doi.org/10.1016/j.neuron.2013.04.014] [PMID: 23623698]
[16]
Kettenmann H, Hanisch U-K, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev 2011; 91(2): 461-553.
[http://dx.doi.org/10.1152/physrev.00011.2010] [PMID: 21527731]
[17]
Cuello AC. Early and late CNS inflammation in Alzheimer’s disease: two extremes of a continuum? Trends Pharmacol Sci 2017; 38(11): 956-66.
[http://dx.doi.org/10.1016/j.tips.2017.07.005] [PMID: 28867259]
[18]
Ji K, Akgul G, Wollmuth LP, Tsirka SE. Microglia actively regulate the number of functional synapses. PLoS One 2013; 8(2)e56293
[http://dx.doi.org/10.1371/journal.pone.0056293] [PMID: 23393609]
[19]
Parkhurst CN, Yang G, Ninan I, et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 2013; 155(7): 1596-609.
[http://dx.doi.org/10.1016/j.cell.2013.11.030] [PMID: 24360280]
[20]
Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 2016; 15(7): 673-84.
[http://dx.doi.org/10.1016/S1474-4422(16)00070-3] [PMID: 27068280]
[21]
Zhu Y, Chai YL, Hilal S, et al. Serum IL-8 is a marker of white-matter hyperintensities in patients with Alzheimer’s disease. Alzheimers Dement (Amst) 2017; 7(1): 41-7.
[http://dx.doi.org/10.1016/j.dadm.2017.01.001] [PMID: 28239640]
[22]
O’Bryant SE, Lista S, Rissman RA, et al. Comparing biological markers of Alzheimer’s disease across blood fraction and platforms: comparing apples to oranges Alzheimers Dement (Amst) 2015; 3(1): 27-34..
[http://dx.doi.org/10.1016/j.dadm.2015.12.003] [PMID: 27019866]
[23]
Graeber MB. Changing face of microglia Science (80- ) 2010; 330(6005): 783-8..
[http://dx.doi.org/10.1126/science.1190929]
[24]
Kim JV, Dustin ML. Innate response to focal necrotic injury inside the blood-brain barrier. J Immunol 2006; 177(8): 5269-77.
[25]
Rupprecht R, Papadopoulos V, Rammes G, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov 2010; 9(12): 971-88.
[http://dx.doi.org/10.1038/nrd3295] [PMID: 21119734]
[26]
Guilarte TR. TSPO in diverse CNS pathologies and psychiatric disease: a critical review and a way forward. Pharmacol Ther 2019; 194: 44-58.
[http://dx.doi.org/10.1016/j.pharmthera.2018.09.003] [PMID: 30189290]
[27]
Papadopoulos V, Baraldi M, Guilarte TR, et al. Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 2006; 27(8): 402-9.
[http://dx.doi.org/10.1016/j.tips.2006.06.005] [PMID: 16822554]
[28]
Guilarte TR, Loth MK, Guariglia SR. TSPO finds NOX2 in microglia for redox homeostasis. Trends Pharmacol Sci 2016; 37(5): 334-43.
[http://dx.doi.org/10.1016/j.tips.2016.02.008] [PMID: 27113160]
[29]
Kreisl WC, Henter ID, Innis RB. Chapter eight - imaging translocator protein as a biomarker of neuroinflammation in dementia. (Eds: Pasternak GW and Coyle JTBT-A in P) Apprentices to Genius: a tribute to Solomon H Snyder. Academic Press 2018; pp. 163-85..
[30]
James ML, Fulton RR, Vercoullie J, et al. DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med 2008; 49(5): 814-22.
[http://dx.doi.org/10.2967/jnumed.107.046151] [PMID: 18413395]
[31]
Imaizumi M, Kim H-J, Zoghbi SS, et al. PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat. Neurosci Lett 2007; 411(3): 200-5.
[http://dx.doi.org/10.1016/j.neulet.2006.09.093] [PMID: 17127001]
[32]
Zhang M-R, Kida T, Noguchi J, et al. [(11)C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brain. Nucl Med Biol 2003; 30(5): 513-9.
[http://dx.doi.org/10.1016/S0969-8051(03)00016-7] [PMID: 12831989]
[33]
Wilson AA, Garcia A, Parkes J, et al. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors. Nucl Med Biol 2008; 35(3): 305-14.
[http://dx.doi.org/10.1016/j.nucmedbio.2007.12.009] [PMID: 18355686]
[34]
Jacobs AH, Tavitian B. INMiND consortium. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab 2012; 32(7): 1393-415.
[http://dx.doi.org/10.1038/jcbfm.2012.53] [PMID: 22549622]
[35]
Venneti S, Lopresti BJ, Wang G, et al. PK11195 labels activated microglia in Alzheimer’s disease and in vivo in a mouse model using PET. Neurobiol Aging 2009; 30(8): 1217-26.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.11.005] [PMID: 18178291]
[36]
Roberts JC, Friel SL, Roman S, et al. Autoradiographical imaging of PPARgamma agonist effects on PBR/TSPO binding in TASTPM mice. Exp Neurol 2009; 216(2): 459-70.
[http://dx.doi.org/10.1016/j.expneurol.2009.01.002] [PMID: 19320004]
[37]
Rapic S, Backes H, Viel T, et al. Imaging microglial activation and glucose consumption in a mouse model of Alzheimer’s disease. Neurobiol Aging 2013; 34(1): 351-4.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.04.016] [PMID: 22651996]
[38]
Heneka MT, Reyes-Irisarri E, Hüll M, Kummer MP. Impact and therapeutic potential of PPARs in Alzheimer’s disease. Curr Neuropharmacol 2011; 9(4): 643-50.
[http://dx.doi.org/10.2174/157015911798376325] [PMID: 22654722]
[39]
Cosenza-Nashat M, Zhao M-L, Suh H-S, et al. Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathol Appl Neurobiol 2009; 35(3): 306-28.
[http://dx.doi.org/10.1111/j.1365-2990.2008.01006.x] [PMID: 19077109]
[40]
Schain M, Kreisl WC. Neuroinflammation in neurodegenerative disorders-a review. Curr Neurol Neurosci Rep 2017; 17(3): 25.
[http://dx.doi.org/10.1007/s11910-017-0733-2] [PMID: 28283959]
[41]
Hamelin L, Lagarde J, Dorothée G, et al. Clinical IMABio3 team. Early and protective microglial activation in Alzheimer’s disease: a prospective study using 18F-DPA-714 PET imaging. Brain 2016; 139(Pt 4): 1252-64.
[http://dx.doi.org/10.1093/brain/aww017] [PMID: 26984188]
[42]
Gerhard A. TSPO imaging in parkinsonian disorders. Clin Transl Imaging 2016; 4(3): 183-90.
[http://dx.doi.org/10.1007/s40336-016-0171-1] [PMID: 27340650]
[43]
Iannaccone S, Cerami C, Alessio M, et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord 2013; 19(1): 47-52.
[http://dx.doi.org/10.1016/j.parkreldis.2012.07.002] [PMID: 22841687]
[44]
Schuitemaker A, Kropholler MA, Boellaard R, et al. Microglial activation in Alzheimer’s disease: an (R)-[11C]PK11195 positron emission tomography study. Neurobiol Aging 2013; 34(1): 128-36.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.04.021] [PMID: 22840559]
[45]
Varrone A, Oikonen V, Forsberg A, et al. Positron emission tomography imaging of the 18-kDa translocator protein (TSPO) with [18F]FEMPA in Alzheimer’s disease patients and control subjects. Eur J Nucl Med Mol Imaging 2015; 42(3): 438-46.
[http://dx.doi.org/10.1007/s00259-014-2955-8] [PMID: 25412766]
[46]
Yasuno F, Ota M, Kosaka J, et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry 2008; 64(10): 835-41.
[http://dx.doi.org/10.1016/j.biopsych.2008.04.021] [PMID: 18514164]
[47]
Gui Y, Marks JD, Das S, Hyman BT, Serrano-Pozo A. Characterization of the 18 kDa translocator protein (TSPO) expression in post-mortem normal and Alzheimer’s disease brains. Brain Pathol 2020; 30(1): 151-64.
[http://dx.doi.org/10.1111/bpa.12763] [PMID: 31276244]
[48]
Suridjan I, Pollock BG, Verhoeff NPLG, et al. In-vivo imaging of grey and white matter neuroinflammation in Alzheimer’s disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA. Mol Psychiatry 2015; 20(12): 1579-87.
[http://dx.doi.org/10.1038/mp.2015.1] [PMID: 25707397]
[49]
Kreisl WC, Lyoo CH, Liow J-S, et al. (11)C-PBR28 binding to translocator protein increases with progression of Alzheimer’s disease. Neurobiol Aging 2016; 44: 53-61.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.04.011] [PMID: 27318133]
[50]
Yokokura M, Mori N, Yagi S, et al. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2011; 38(2): 343-51.
[http://dx.doi.org/10.1007/s00259-010-1612-0] [PMID: 20844871]
[51]
Fan Z, Aman Y, Ahmed I, et al. Influence of microglial activation on neuronal function in Alzheimer’s and Parkinson’s disease dementia. Alzheimers Dement 2015; 11(6): 608-21.e7.
[http://dx.doi.org/10.1016/j.jalz.2014.06.016] [PMID: 25239737]
[52]
Edison P, Archer HA, Hinz R, et al. Amyloid, hypometabolism, and cognition in Alzheimer disease. Neurology 2007; 68(7): 501-8.
[53]
Kreisl WC, Lyoo CH, McGwier M, et al. Biomarkers consortium PET radioligand project team. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease. Brain 2013; 136(Pt 7): 2228-38.
[http://dx.doi.org/10.1093/brain/awt145] [PMID: 23775979]
[54]
Okello A, Edison P, Archer HA, et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 2009; 72(1): 56-62.
[http://dx.doi.org/10.1212/01.wnl.0000338622.27876.0d] [PMID: 19122031]
[55]
Yasuno F, Kosaka J, Ota M, et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with ["C]DAA1106. Psychiatry Res 2012; 203(1): 67-74.
[http://dx.doi.org/10.1016/j.pscychresns.2011.08.013] [PMID: 22892349]
[56]
Dupont A-C, Largeau B, Santiago Ribeiro MJ, Guilloteau D, Tronel C, Arlicot N. Translocator protein-18 kDa (TSPO) positron emission tomography (PET) imaging and its clinical impact in neurodegenerative diseases. Int J Mol Sci 2017; 18(4): 1-37.
[http://dx.doi.org/10.3390/ijms18040785] [PMID: 28387722]
[57]
Cagnin A, Brooks DJ, Kennedy AM, et al. In-vivo measurement of activated microglia in dementia. Lancet 2001; 358(9280): 461-7.
[http://dx.doi.org/10.1016/S0140-6736(01)05625-2] [PMID: 11513911]
[58]
Wiley CA, Lopresti BJ, Venneti S, et al. Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol 2009; 66(1): 60-7.
[http://dx.doi.org/10.1001/archneurol.2008.511] [PMID: 19139300]
[59]
Varrone A, Mattsson P, Forsberg A, et al. In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer’s disease patients. Eur J Nucl Med Mol Imaging 2013; 40(6): 921-31.
[http://dx.doi.org/10.1007/s00259-013-2359-1] [PMID: 23436070]
[60]
Golla SSV, Boellaard R, Oikonen V, et al. Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer’s disease patients. J Cereb Blood Flow Metab 2015; 35(5): 766-72.
[http://dx.doi.org/10.1038/jcbfm.2014.261] [PMID: 25649991]
[61]
Janssen B, Mach RH. Chapter 7 - Development of brain PET imaging agents: strategies for imaging neuroinflammation in Alzheimer’s disease.(Eds: Becker JT and Cohen ADBT-P in MB and TS) Brain Imaging. Academic Press 2019; pp. 371-99..
[62]
Notter T, Schalbetter SM, Clifton NE, et al. Neuronal activity increases translocator protein (TSPO) levels. Mol Psychiatry 2020.
[http://dx.doi.org/10.1038/s41380-020-0745-1] [PMID: 32398717]
[63]
Chauveau F, Boutin H, Van Camp N, et al. In vivo imaging of neuroinflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa). Eur J Nucl Med Mol Imaging 2011; 38(3): 509-14.
[http://dx.doi.org/10.1007/s00259-010-1628-5] [PMID: 20936410]
[64]
Chauveau F, Van Camp N, Dollé F, et al. Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation. J Nucl Med 2009; 50(3): 468-76.
[http://dx.doi.org/10.2967/jnumed.108.058669] [PMID: 19223401]
[65]
Schmid CD, Sautkulis LN, Danielson PE, et al. Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J Neurochem 2002; 83(6): 1309-20.
[http://dx.doi.org/10.1046/j.1471-4159.2002.01243.x] [PMID: 12472885]
[66]
Hsieh CL, Koike M, Spusta SC, et al. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem 2009; 109(4): 1144-56.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06042.x] [PMID: 19302484]
[67]
Takahashi K, Rochford CDP, Neumann H. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med 2005; 201(4): 647-57.
[http://dx.doi.org/10.1084/jem.20041611] [PMID: 15728241]
[68]
Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE, Lanier LL. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol 2006; 177(4): 2051-5.
[http://dx.doi.org/10.4049/jimmunol.177.4.2051] [PMID: 16887962]
[69]
Colonna M, Wang Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat Rev Neurosci 2016; 17(4): 201-7.
[http://dx.doi.org/10.1038/nrn.2016.7] [PMID: 26911435]
[70]
Zhong L, Chen X-F, Wang T, et al. Soluble TREM2 induces inflammatory responses and enhances microglial survival. J Exp Med 2017; 214(3): 597-607.
[http://dx.doi.org/10.1084/jem.20160844] [PMID: 28209725]
[71]
Wang Y, Cella M, Mallinson K, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 2015; 160(6): 1061-71.
[http://dx.doi.org/10.1016/j.cell.2015.01.049] [PMID: 25728668]
[72]
Frank S, Burbach GJ, Bonin M, et al. TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia 2008; 56(13): 1438-47.
[http://dx.doi.org/10.1002/glia.20710] [PMID: 18551625]
[73]
Xiang X, Werner G, Bohrmann B, et al. TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance. EMBO Mol Med 2016; 8(9): 992-1004.
[http://dx.doi.org/10.15252/emmm.201606370] [PMID: 27402340]
[74]
Jonsson T, Stefansson H, Steinberg S, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 2013; 368(2): 107-16.
[http://dx.doi.org/10.1056/NEJMoa1211103] [PMID: 23150908]
[75]
Jin SC, Benitez BA, Karch CM, et al. Coding variants in TREM2 increase risk for Alzheimer’s disease. Hum Mol Genet 2014; 23(21): 5838-46.
[http://dx.doi.org/10.1093/hmg/ddu277] [PMID: 24899047]
[76]
Guerreiro R, Wojtas A, Bras J, et al. Alzheimer genetic analysis group. TREM2 variants in Alzheimer’s disease. N Engl J Med 2013; 368(2): 117-27.
[http://dx.doi.org/10.1056/NEJMoa1211851] [PMID: 23150934]
[77]
Slattery CF, Beck J, Harper L, et al. trem2 variants increase risk of typical early-onset Alzheimer’s disease but not of prion or frontotemporal dementia. J Neurol Neurosurg Psychiatry 2014; 85(8): e3.
[http://dx.doi.org/10.1136/jnnp-2014-308883.7]
[78]
Lill CM, Rengmark A, Pihlstrøm L, et al. SLAGEN Consortium. The role of TREM2 R47H as a risk factor for Alzheimer’s disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson’s disease. Alzheimers Dement 2015; 11(12): 1407-16.
[http://dx.doi.org/10.1016/j.jalz.2014.12.009] [PMID: 25936935]
[79]
Piccio L, Deming Y, Del-Águila JL, et al. Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol 2016; 131(6): 925-33.
[http://dx.doi.org/10.1007/s00401-016-1533-5] [PMID: 26754641]
[80]
Wilson EN, Swarovski MS, Linortner P, et al. Soluble TREM2 is elevated in Parkinson’s disease subgroups with increased CSF tau. Brain 2020; 143(3): 932-43.
[http://dx.doi.org/10.1093/brain/awaa021] [PMID: 32065223]
[81]
Suárez-Calvet M, Araque Caballero MÁ, Kleinberger G, et al. Dominantly Inherited Alzheimer Network. Early changes in CSF sTREM2 in dominantly inherited Alzheimer’s disease occur after amyloid deposition and neuronal injury. Sci Transl Med 2016; 8(369)369ra178
[http://dx.doi.org/10.1126/scitranslmed.aag1767] [PMID: 27974666]
[82]
Suárez-Calvet M, Kleinberger G, Araque Caballero MÁ, et al. sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer’s disease and associate with neuronal injury markers. EMBO Mol Med 2016; 8(5): 466-76.
[http://dx.doi.org/10.15252/emmm.201506123] [PMID: 26941262]
[83]
Gispert JD, Monté GC, Suárez-Calvet M, et al. The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer’s disease but not those of sTREM2. Alzheimers Dement (Amst) 2016; 6(1): 50-9.
[http://dx.doi.org/10.1016/j.dadm.2016.12.002] [PMID: 28149943]
[84]
Heslegrave A, Heywood W, Paterson R, et al. Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease. Mol Neurodegener 2016; 11(3): 3.
[http://dx.doi.org/10.1186/s13024-016-0071-x] [PMID: 26754172]
[85]
Schindler SE, Holtzman DM. CSF sTREM2: marking the tipping point between preclinical AD and dementia? EMBO Mol Med 2016; 8(5): 437-8.
[http://dx.doi.org/10.15252/emmm.201606245] [PMID: 26976613]
[86]
Gispert JD, Suárez-Calvet M, Monté GC, et al. Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer’s disease. Alzheimers Dement 2016; 12(12): 1259-72.
[http://dx.doi.org/10.1016/j.jalz.2016.06.005] [PMID: 27423963]
[87]
Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull 2006; 53(2): 172-209.
[PMID: 17087877]
[88]
Johansen JS, Williamson MK, Rice JS, Price PA. Identification of proteins secreted by human osteoblastic cells in culture. J Bone Miner Res 1992; 7(5): 501-12.
[http://dx.doi.org/10.1002/jbmr.5650070506] [PMID: 1615759]
[89]
Kazakova MH, Sarafian VS. YKL-40--a novel biomarker in clinical practice? Folia Med (Plovdiv) 2009; 51(1): 5-14.
[PMID: 19437893]
[90]
Bonneh-Barkay D, Wang G, Starkey A, Hamilton RL, Wiley CA. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. J Neuroinflammation 2010; 7(1): 34-41.
[http://dx.doi.org/10.1186/1742-2094-7-34] [PMID: 20540736]
[91]
Colton CA, Mott RT, Sharpe H, Xu Q, Van Nostrand WE, Vitek MP. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J Neuroinflammation 2006; 3(1): 27.
[http://dx.doi.org/10.1186/1742-2094-3-27] [PMID: 17005052]
[92]
Gispert JD, Monté GC, Falcon C, et al. CSF YKL-40 and pTau181 are related to different cerebral morphometric patterns in early AD. Neurobiol Aging 2016; 38: 47-55.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.10.022] [PMID: 26827642]
[93]
Alcolea D, Vilaplana E, Pegueroles J, et al. Relationship between cortical thickness and cerebrospinal fluid YKL-40 in predementia stages of Alzheimer’s disease. Neurobiol Aging 2015; 36(6): 2018-23.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.03.001] [PMID: 25865441]
[94]
Hellwig K, Kvartsberg H, Portelius E, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther 2015; 7(1): 74-81.
[http://dx.doi.org/10.1186/s13195-015-0161-y] [PMID: 26698298]
[95]
Kester MI, Teunissen CE, Sutphen C, et al. Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer’s disease in a memory clinic cohort. Alzheimers Res Ther 2015; 7(1): 59-67.
[http://dx.doi.org/10.1186/s13195-015-0142-1] [PMID: 26383836]
[96]
Antonell A, Mansilla A, Rami L, et al. Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer’s disease. J Alzheimers Dis 2014; 42(3): 901-8.
[http://dx.doi.org/10.3233/JAD-140624] [PMID: 25024322]
[97]
Wennström M, Surova Y, Hall S, et al. The inflammatory marker YKL-40 is elevated in cerebrospinal fluid from patients with Alzheimer’s but not Parkinson’s disease or dementia with lewy bodies. PLoS One 2015; 10(8)e0135458
[http://dx.doi.org/10.1371/journal.pone.0135458] [PMID: 26270969]
[98]
Sutphen CL, Jasielec MS, Shah AR, et al. Longitudinal cerebrospinal fluid biomarker changes in preclinical Alzheimer disease during middle age. JAMA Neurol 2015; 72(9): 1029-42.
[http://dx.doi.org/10.1001/jamaneurol.2015.1285] [PMID: 26147946]
[99]
Höglund K, Kern S, Zettergren A, et al. Preclinical amyloid pathology biomarker positivity: effects on tau pathology and neurodegeneration. Transl Psychiatry 2017; 7(1): e995-5.
[http://dx.doi.org/10.1038/tp.2016.252] [PMID: 28072416]
[100]
Wyss-Coray T, Loike JD, Brionne TC, et al. Adult mouse astrocytes degrade amyloid-β in vitro and in situ. Nat Med 2003; 9(4): 453-7.
[http://dx.doi.org/10.1038/nm838] [PMID: 12612547]
[101]
El Khoury J, Toft M, Hickman SE, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 2007; 13(4): 432-8.
[http://dx.doi.org/10.1038/nm1555] [PMID: 17351623]
[102]
Forloni G, Mangiarotti F, Angeretti N, Lucca E, De Simoni MG. β-amyloid fragment potentiates IL-6 and TNF-α secretion by LPS in astrocytes but not in microglia. Cytokine 1997; 9(10): 759-62.
[http://dx.doi.org/10.1006/cyto.1997.0232] [PMID: 9344508]
[103]
Corrêa JD, Starling D, Teixeira AL, Caramelli P, Silva TA. Chemokines in CSF of Alzheimer’s disease patients. Arq Neuropsiquiatr 2011; 69(3): 455-9.
[http://dx.doi.org/10.1590/S0004-282X2011000400009] [PMID: 21755121]
[104]
Galimberti D, Schoonenboom N, Scheltens P, et al. Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol 2006; 63(4): 538-43.
[http://dx.doi.org/10.1001/archneur.63.4.538] [PMID: 16606766]
[105]
Blasko I, Lederer W, Oberbauer H, et al. Measurement of thirteen biological markers in CSF of patients with Alzheimer’s disease and other dementias. Dement Geriatr Cogn Disord 2006; 21(1): 9-15.
[http://dx.doi.org/10.1159/000089137] [PMID: 16244482]
[106]
Westin K, Buchhave P, Nielsen H, Minthon L, Janciauskiene S, Hansson O. CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer’s disease. PLoS One 2012; 7(1): e30525-5.
[http://dx.doi.org/10.1371/journal.pone.0030525] [PMID: 22303443]
[107]
Janelidze S, Mattsson N, Stomrud E, et al. CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease. Neurology 2018; 91(9): 867-77.
[http://dx.doi.org/10.1212/WNL.0000000000006082]
[108]
Shrestha R, Millington O, Brewer J, Bushell T. Is central nervous system an immune-privileged site? Kathmandu Univ Med J(KUMJ) 2013; 11(41): 102-7.
[PMID: 23774427]
[109]
Cunningham C. Microglia and neurodegeneration: the role of systemic inflammation. Glia 2013; 61(1): 71-90.
[http://dx.doi.org/10.1002/glia.22350] [PMID: 22674585]
[110]
Holmes C, Butchart J. Systemic inflammation and Alzheimer’s disease. Biochem Soc Trans 2011; 39(4): 898-901.
[http://dx.doi.org/10.1042/BST0390898] [PMID: 21787320]
[111]
Quan N, Banks WA. Brain-immune communication pathways. Brain Behav Immun 2007; 21(6): 727-35.
[http://dx.doi.org/10.1016/j.bbi.2007.05.005] [PMID: 17604598]
[112]
Greenberg SM, Gurol ME, Rosand J, Smith EE. M. GS. Amyloid angiopathy-related vascular cognitive impairment. Stroke 2004; 35(11)(1): 2616-9..
[http://dx.doi.org/10.1161/01.STR.0000143224.36527.44] [PMID: 15459438]
[113]
Kinnecom C, Lev MH, Wendell L, et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology 2007; 68(17): 1411-6.
[http://dx.doi.org/10.1212/01.wnl.0000260066.98681.2e] [PMID: 17452586]
[114]
Takeda S, Sato N, Morishita R. Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Front Aging Neurosci 2014; 6: 171-9.
[http://dx.doi.org/10.3389/fnagi.2014.00171] [PMID: 25120476]
[115]
Su C, Zhao K, Xia H, Xu Y. Peripheral inflammatory biomarkers in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. Psychogeriatrics 2019; 19(4): 300-9.
[http://dx.doi.org/10.1111/psyg.12403] [PMID: 30790387]
[116]
Darweesh SKL, Wolters FJ, Ikram MA, de Wolf F, Bos D, Hofman A. Inflammatory markers and the risk of dementia and Alzheimer’s disease: A meta-analysis. Alzheimers Dement 2018; 14(11): 1450-9.
[http://dx.doi.org/10.1016/j.jalz.2018.02.014] [PMID: 29605221]
[117]
Lai KSP, Liu CS, Rau A, et al. Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 2017; 88(10): 876-82.
[http://dx.doi.org/10.1136/jnnp-2017-316201] [PMID: 28794151]
[118]
Gong C, Wei D, Wang Y, et al. A meta-analysis of c-reactive protein in patients with Alzheimer’s disease. Am J Alzheimers Dis Other Demen 2016; 31(3): 194-200.
[http://dx.doi.org/10.1177/1533317515602087] [PMID: 26340961]
[119]
Koyama A, O’Brien J, Weuve J, Blacker D, Metti AL, Yaffe K. The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis. J Gerontol A Biol Sci Med Sci 2013; 68(4): 433-40.
[http://dx.doi.org/10.1093/gerona/gls187] [PMID: 22982688]
[120]
Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 2010; 68(10): 930-41.
[http://dx.doi.org/10.1016/j.biopsych.2010.06.012] [PMID: 20692646]
[121]
Shen X-N, Niu L-D, Wang Y-J, et al. Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. J Neurol Neurosurg Psychiatry 2019; 90(5): 590-8.
[http://dx.doi.org/10.1136/jnnp-2018-319148] [PMID: 30630955]
[122]
Hu WT, Holtzman DM, Fagan AM, et al. Alzheimer’s Disease Neuroimaging Initiative. Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease. Neurology 2012; 79(9): 897-905.
[http://dx.doi.org/10.1212/WNL.0b013e318266fa70] [PMID: 22855860]
[123]
Ray S, Britschgi M, Herbert C, et al. Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med 2007; 13(11): 1359-62.
[http://dx.doi.org/10.1038/nm1653] [PMID: 17934472]
[124]
Soares HD, Potter WZ, Pickering E, et al. Biomarkers consortium Alzheimer’s disease plasma proteomics project. Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch Neurol 2012; 69(10): 1310-7.
[http://dx.doi.org/10.1001/archneurol.2012.1070] [PMID: 22801723]
[125]
Britschgi M, Rufibach K, Huang SLB, et al. Modeling of pathological traits in Alzheimer's disease based on systemic extracellular signaling proteome Mol & Cell Proteomics 2011; 10(10): M111.008862..
[126]
Johnstone D, Milward EA, Berretta R, Moscato P, Initiative ADN. Alzheimer’s Disease Neuroimaging Initiative. Multivariate protein signatures of pre-clinical Alzheimer’s disease in the Alzheimer’s disease neuroimaging initiative (ADNI) plasma proteome dataset. PLoS One 2012; 7(4): e34341-1.
[http://dx.doi.org/10.1371/journal.pone.0034341] [PMID: 22485168]
[127]
Rogers J, Kirby LC, Hempelman SR, et al. Clinical trial of indomethacin in Alzheimer’s disease. Neurology 1993; 43(8): 1609-11.
[http://dx.doi.org/10.1212/WNL.43.8.1609] [PMID: 8351023]
[128]
de Jong D, Jansen R, Hoefnagels W, et al. No effect of one-year treatment with indomethacin on Alzheimer’s disease progression: a randomized controlled trial. PLoS One 2008; 3(1): e1475-5.
[http://dx.doi.org/10.1371/journal.pone.0001475] [PMID: 18213383]
[129]
Thal LJ, Ferris SH, Kirby L, et al. Rofecoxib Protocol 078 study group. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 2005; 30(6): 1204-15.
[http://dx.doi.org/10.1038/sj.npp.1300690] [PMID: 15742005]
[130]
Aisen PS, Schafer KA, Grundman M, et al. Alzheimer’s Disease Cooperative Study. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003; 289(21): 2819-26.
[http://dx.doi.org/10.1001/jama.289.21.2819] [PMID: 12783912]
[131]
Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease. Neurology 1999; 53(1): 197-201.
[http://dx.doi.org/10.1212/WNL.53.1.197] [PMID: 10408559]
[132]
Aisen PS, Davis KL, Berg JD, et al. A randomized controlled trial of prednisone in Alzheimer’s disease. Alzheimer’s Disease Cooperative Study. Neurology 2000; 54(3): 588-93.
[http://dx.doi.org/10.1212/WNL.54.3.588] [PMID: 10680787]
[133]
Bentham P, Gray R, Sellwood E, Hills R, Crome P, Raftery J. AD2000 Collaborative Group. Aspirin in Alzheimer’s disease (AD2000): a randomised open-label trial. Lancet Neurol 2008; 7(1): 41-9.
[http://dx.doi.org/10.1016/S1474-4422(07)70293-4] [PMID: 18068522]
[134]
Van Gool WA, Weinstein HC, Scheltens P, Walstra GJM. Effect of hydroxychloroquine on progression of dementia in early Alzheimer’s disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet 2001; 358(9280): 455-60.
[http://dx.doi.org/10.1016/S0140-6736(01)05623-9] [PMID: 11513909]
[135]
Meinert CL, McCaffrey LD, Breitner JC. ADAPT Research Group. Alzheimer’s Disease Anti-inflammatory Prevention Trial: design, methods, and baseline results. Alzheimers Dement 2009; 5(2): 93-104.
[http://dx.doi.org/10.1016/j.jalz.2008.09.004] [PMID: 19328435]
[136]
Solomon SD, McMurray JJV, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352(11): 609-19.
[137]
Breitner JC, Baker LD, Montine TJ, et al. ADAPT Research Group. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement 2011; 7(4): 402-11.
[http://dx.doi.org/10.1016/j.jalz.2010.12.014] [PMID: 21784351]
[138]
Leoutsakos J-MS, Muthen BO, Breitner JCS, Lyketsos CG. ADAPT Research Team. Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer’s Disease Anti-inflammatory Prevention Trial. Int J Geriatr Psychiatry 2012; 27(4): 364-74.
[PMID: 21560159]
[139]
Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer’s disease and duration of NSAID use. Neurology 1997; 48(3): 626-32.
[http://dx.doi.org/10.1212/WNL.48.3.626] [PMID: 9065537]
[140]
Zandi PP, Breitner JCS, Anthony JC. Is pharmacological prevention of Alzheimer’s a realistic goal? Expert Opin Pharmacother 2002; 3(4): 365-80.
[http://dx.doi.org/10.1517/14656566.3.4.365] [PMID: 11934339]
[141]
Pasqualetti P, Bonomini C, Dal Forno G, et al. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease. Aging Clin Exp Res 2009; 21(2): 102-10.
[http://dx.doi.org/10.1007/BF03325217] [PMID: 19448381]
[142]
McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol 2013; 126(4): 479-97.
[http://dx.doi.org/10.1007/s00401-013-1177-7] [PMID: 24052108]
[143]
Rogers J. Principles for central nervous system inflammation research: a call for a consortium approach. Alzheimers Dement 2018; 14(11): 1553-9.
[http://dx.doi.org/10.1016/j.jalz.2018.01.008] [PMID: 29494807]
[144]
Fotuhi M, Zandi PP, Hayden KM, et al. Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study. Alzheimers Dement 2008; 4(3): 223-7.
[http://dx.doi.org/10.1016/j.jalz.2008.01.004] [PMID: 18631971]
[145]
Szekely CA, Breitner JCS, Fitzpatrick AL, et al. NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type. Neurology 2008; 70(1): 17-24.
[http://dx.doi.org/10.1212/01.wnl.0000284596.95156.48] [PMID: 18003940]
[146]
Sweet RA, Seltman H, Emanuel JE, et al. Effect of Alzheimer’s disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study. Am J Psychiatry 2012; 169(9): 954-62.
[http://dx.doi.org/10.1176/appi.ajp.2012.11121815] [PMID: 22952074]
[147]
Sudduth TL, Schmitt FA, Nelson PT, Wilcock DM. Neuroinflammatory phenotype in early Alzheimer’s disease. Neurobiol Aging 2013; 34(4): 1051-9.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.09.012] [PMID: 23062700]
[148]
Bäckman L, Jones S, Small BJ, Agüero-Torres H, Fratiglioni L. Rate of cognitive decline in preclinical Alzheimer’s disease: the role of comorbidity. J Gerontol B Psychol Sci Soc Sci 2003; 58(4): 228-36.
[http://dx.doi.org/10.1093/geronb/58.4.P228] [PMID: 12878651]
[149]
Leoutsakos J-MS, Han D, Mielke MM, et al. Effects of general medical health on Alzheimer’s progression: the Cache County Dementia Progression Study. Int Psychogeriatr 2012; 24(10): 1561-70.
[http://dx.doi.org/10.1017/S104161021200049X] [PMID: 22687143]
[150]
Latta CH, Brothers HM, Wilcock DM. Neuroinflammation in Alzheimer’s disease; a source of heterogeneity and target for personalized therapy. Neuroscience 2015; 302: 103-11.
[http://dx.doi.org/10.1016/j.neuroscience.2014.09.061] [PMID: 25286385]

Rights & Permissions Print Cite
Article Metrics
62
© 2024 Bentham Science Publishers | Privacy Policy