Abstract
Alzheimer's disease (AD) is a psychological, biological, or developmental disorder that affects basic mental functioning. AD is generally affiliated with marked discomfort and impaired social, professional, or other crucial aspects of life. AD is predominant worldwide, but a disparity in prevalence is observed amongst nations. Around 3/4 of people with Alzheimer's disease are from underdeveloped nations, which receive only 1/10th of global mental health resources. Residents of each community and age category share their presence in the overall load of AD. AD is a multifactorial disease impacted by numerous environmental, genetic, and endogenous elements. Heteromorphic interactive downstream cascades, networks, and molecular mechanisms (inflammation and immune network, cholinergic deficit, lipid transit, endocytosis, excitotoxicity, oxidative stress, amyloid and tau pathology, energy metabolism, neuron and synapse loss, and cell death) have been isolated, imparting a non-dissociative contribution in pathogenesis of AD. In the CNS, the structural organization of cholinergic neurons can give a novel insight into the mechanism of new learning. The alleviation of central cholinergic transposal following destruction in the basal forebrain cholinergic neurons precipitates a decline in neurocognitive symptoms visible in AD patients. The brain of patients suffering from AD exhibits plaques of aggregated amyloid-β and neurofibrillary tangles containing hyperphosphorylated tau protein. Amyloid-β triggers cholinergic loss by modulation of calcium and generation of cell-damaging molecules such as nitric oxide and reactive oxygen species intermediates. The present review focuses on the pathogenic mechanisms related to stages, diagnosis, and therapeutic approaches involved in AD.
Keywords: Alzheimer’s disease, oxidative stress, inflammation, amyloidogenic, tauopathy, cholinergic deficits, memory, dementia.
[http://dx.doi.org/10.31887/DCNS.2013.15.4/hjahn] [PMID: 24459411]
[http://dx.doi.org/10.3390/biom6010006] [PMID: 26751493]
[http://dx.doi.org/10.1016/S1474-4422(18)30403-4] [PMID: 30497964]
[http://dx.doi.org/10.1017/cjn.2016.36] [PMID: 27307128]
[http://dx.doi.org/10.1016/j.ejmech.2020.112915] [PMID: 33139110]
[http://dx.doi.org/10.3390/ijms17040503] [PMID: 27058526]
[http://dx.doi.org/10.1016/j.bbr.2012.12.005] [PMID: 23238038]
[http://dx.doi.org/10.1515/revneuro-2017-0006] [PMID: 28704198]
[http://dx.doi.org/10.1590/S1980-57642011DN05030002] [PMID: 29213739]
[http://dx.doi.org/10.11919/j.issn.1002-0829.215001] [PMID: 26120262]
[http://dx.doi.org/10.1111/joim.12178] [PMID: 24605807]
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606]
[http://dx.doi.org/10.3390/ijms21061989] [PMID: 32183332]
[http://dx.doi.org/10.1016/j.neuron.2016.09.006]
[http://dx.doi.org/10.1016/j.neuron.2012.08.036] [PMID: 23040810]
[http://dx.doi.org/10.1007/7854_2016_467]
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[http://dx.doi.org/10.3389/fnins.2019.00446] [PMID: 31133787]
[http://dx.doi.org/10.1007/978-3-030-74046-7_10] [PMID: 34453297]
[http://dx.doi.org/10.1111/jnc.14052] [PMID: 28791706]
[http://dx.doi.org/10.3390/biom10010040] [PMID: 31888102]
[http://dx.doi.org/10.3233/JAD-160763] [PMID: 27662322]
[http://dx.doi.org/10.3389/fnins.2019.00043] [PMID: 30800052]
[http://dx.doi.org/10.3390/ijms21207452] [PMID: 33050345]
[http://dx.doi.org/10.1177/1759091419855541] [PMID: 31213067]
[http://dx.doi.org/10.1016/j.pharmthera.2022.108122] [PMID: 35114285]
[http://dx.doi.org/10.1523/JNEUROSCI.2039-21.2021]
[http://dx.doi.org/10.1038/srep38187] [PMID: 27917876]
[http://dx.doi.org/10.1186/s13578-021-00712-3] [PMID: 34895338]
[http://dx.doi.org/10.1021/cn500148z] [PMID: 25268947]
[http://dx.doi.org/10.1038/nrneurol.2015.225] [PMID: 26635213]
[http://dx.doi.org/10.1016/j.celrep.2021.109419] [PMID: 34289368]
[http://dx.doi.org/10.3389/fnagi.2017.00083] [PMID: 28420982]
[http://dx.doi.org/10.3389/fnmol.2020.00155] [PMID: 32973448]
[http://dx.doi.org/10.1073/pnas.2021461118] [PMID: 33952699]
[http://dx.doi.org/10.1038/s41582-020-00435-y] [PMID: 33318676]
[http://dx.doi.org/10.1186/s13024-020-00391-7] [PMID: 32677986]
[http://dx.doi.org/10.1016/j.trci.2016.05.001] [PMID: 29067297]
[http://dx.doi.org/10.1016/j.febslet.2014.05.046] [PMID: 24911209]
[http://dx.doi.org/10.1186/alzrt24] [PMID: 20122289]
[http://dx.doi.org/10.2174/1871527316666170807130011] [PMID: 28782486]
[http://dx.doi.org/10.1016/j.neuroscience.2012.02.046] [PMID: 22441036]
[http://dx.doi.org/10.1017/S1461145711000149] [PMID: 21329555]
[http://dx.doi.org/10.1111/jnc.14687] [PMID: 30802950]
[http://dx.doi.org/10.1007/s12035-021-02611-7] [PMID: 34699027]
[http://dx.doi.org/10.3390/biom10010137] [PMID: 31947676]
[http://dx.doi.org/10.1007/s12192-021-01231-3] [PMID: 34386944]
[http://dx.doi.org/10.1155/2012/646354] [PMID: 21977319]
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.09.027] [PMID: 23044265]
[http://dx.doi.org/10.1155/2014/360438] [PMID: 24999379]
[http://dx.doi.org/10.3390/antiox9111128] [PMID: 33202952]
[http://dx.doi.org/10.1007/s11064-017-2456-9] [PMID: 29264677]
[http://dx.doi.org/10.1089/ars.2020.8129] [PMID: 33637005]
[http://dx.doi.org/10.3892/br.2016.630] [PMID: 27123241]
[http://dx.doi.org/10.1016/j.bbadis.2011.10.003] [PMID: 22015471]
[http://dx.doi.org/10.1038/s41573-021-00233-1] [PMID: 34194012]
[http://dx.doi.org/10.1007/s00204-015-1517-6] [PMID: 25895140]
[http://dx.doi.org/10.1016/j.bbrc.2011.11.047] [PMID: 22120629]
[http://dx.doi.org/10.1016/j.trci.2018.09.002] [PMID: 31194101]
[http://dx.doi.org/10.3390/antiox9010061] [PMID: 31936711]
[http://dx.doi.org/10.2174/1566524019666191129103117] [PMID: 31782366]
[http://dx.doi.org/10.3233/JAD-210497] [PMID: 34420962]
[http://dx.doi.org/10.1016/j.bbadis.2013.10.015] [PMID: 24189435]
[http://dx.doi.org/10.3233/JAD-180903] [PMID: 30741683]
[http://dx.doi.org/10.1016/j.gendis.2020.11.008] [PMID: 34522714]
[http://dx.doi.org/10.3390/md19080410] [PMID: 34436249]
[http://dx.doi.org/10.1016/j.ecoenv.2021.112511] [PMID: 34273848]
[http://dx.doi.org/10.1007/s00213-021-05837-4] [PMID: 34173034]
[http://dx.doi.org/10.1021/acs.jmedchem.1c00489] [PMID: 34081466]
[http://dx.doi.org/10.3390/md19040203] [PMID: 33916819]
[http://dx.doi.org/10.4103/1673-5374.274341] [PMID: 31997821]
[http://dx.doi.org/10.1016/S1474-4422(13)70276-X] [PMID: 24556009]
[http://dx.doi.org/10.1016/j.lfs.2021.119964] [PMID: 34537230]
[http://dx.doi.org/10.1111/j.1471-4159.2011.07459.x] [PMID: 21883223]
[http://dx.doi.org/10.3390/molecules25030646] [PMID: 32028607]
[PMID: 27338066]
[http://dx.doi.org/10.3390/molecules26102843] [PMID: 34064783]
[http://dx.doi.org/10.3390/ph12010041] [PMID: 30893882]
[http://dx.doi.org/10.3389/fnagi.2014.00114] [PMID: 24959143]
[http://dx.doi.org/10.3389/fnmol.2020.00137] [PMID: 32848600]
[http://dx.doi.org/10.34133/2019/5341375] [PMID: 31549066]
[http://dx.doi.org/10.1111/bph.14593] [PMID: 30710367]
[http://dx.doi.org/10.1136/bmj.m3684] [PMID: 33036984]
[http://dx.doi.org/10.1002/trc2.12044] [PMID: 32671184]
[http://dx.doi.org/10.3390/ijms21249677] [PMID: 33352989]
[http://dx.doi.org/10.1517/14656566.2016.1146686] [PMID: 26809554]
[http://dx.doi.org/10.3389/fnmol.2020.590896] [PMID: 33343298]
[http://dx.doi.org/10.1038/s41467-019-11674-z] [PMID: 31434879]
[http://dx.doi.org/10.14283/jpad.2018.18] [PMID: 29616709]
[http://dx.doi.org/10.1248/bpb.b17-00091] [PMID: 28458340]
[http://dx.doi.org/10.1016/j.biopsych.2017.08.010] [PMID: 28967385]
[http://dx.doi.org/10.1002/trc2.12050] [PMID: 32695874]
[http://dx.doi.org/10.1016/j.biopsych.2020.02.001] [PMID: 32223911]
[http://dx.doi.org/10.3389/fimmu.2020.01967] [PMID: 33013850]
[http://dx.doi.org/10.1186/alzrt237] [PMID: 24476230]
[http://dx.doi.org/10.2174/1568026620666200422105156] [PMID: 32321405]
[http://dx.doi.org/10.1080/17460441.2019.1667329] [PMID: 31526140]
[http://dx.doi.org/10.1021/jm201332p] [PMID: 22420626]
[http://dx.doi.org/10.3390/ijms20081829] [PMID: 31013856]
[http://dx.doi.org/10.1038/s41582-018-0013-z] [PMID: 29895964]
[http://dx.doi.org/10.2174/1566524021666210406121807] [PMID: 33823777]
[http://dx.doi.org/10.3122/jabfm.2018.01.170270] [PMID: 29330248]