molecular pathology of Alzheimer's disease
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Pathology
- increased formation & deposition of amyloid
- formation & acummulation of intracellular A4/42 is the earliest event in AD[21]
- may be a feature in common with traumatic brain injury
- diminished expression of retromer complex may play role in accumulation of A4/42[12]
- apolipoprotein E binds to the A4/42 amyloid peptide
- enhanced deposition of amyloid A4/42 peptide with apo E4 genotype[8]
- A4/42 accumulates in neurons & astrocytes
- astrocytic A4/42 of neuronal origin
- prion protein PrPc (CD230) may bind & internalize A4 oligomers[13]
- in a study of a mouse model for AD, it is proposed that Abeta may exert on the CRF receptor resulting in damage to the hippocampus resulting from increased corticosteroid release in response to minor stress[22]
- higher CSF A-beta42 increases likelihood of higher neurofibrillary tangles outside of the mesial temporal lobes[23]
- lower CSF A-beta42 increases likelihood of AD[40]
- hyperphosphorylation of microtubule-associated protein tau
- disulfide linkage of hyperphosphorylated tau may be linked to oxidative stress
- formation of paired helical filaments (PHF) from PHF-tau
- see microtubule-associated protein tau for protein kinases that phosphorylate tau
- formation of intracellar A4/42 is upstream of formation of PHF-tau[21]
- newly synthesized tau is truncated & actively released into CSF during neuronal activity associated with presynaptic glutamine release
- rate of truncated forms of tau released into CSF positively correlates with amyloid plaque burden[26]
- isomerization of aspartic acid in a peptide from tau[36]
- increase in isomer found in both autosomal dominant & sporadic AD
- increase consistent with reduced autophagic flux in AD
- increase in isomer found in both autosomal dominant & sporadic AD
- tau oligomer-containing synapses are engulfed by microglia & astrocytes in Braak stage 3-4 Alzheimer's dementia in the absence of neurofibrillary tangle deposition[43]
- CSF soluble TREM2 & TREM2 expressed on microglia may play a role in facilitation of PHF-tau propagation by activated microglia in association with beta-amyloid[34]
- microglial activation & PHF-tau propagate jointly across Braak stages
- expression of TREM2 rises in parallel with expression of beta-amyloid in the cerebral cortex
- PERK kinase (EIF2AK3) & the unfolded protein response may be associated with tau pathology
- activation of inflammatory mediators
- activation of the complement system
- interaction of A4-beta peptide with C1q[2]
- activation of C4 by A4-beta peptide[3]
- complement activation by tau[4]
- upregulation of C-reactive protein in CSF[5]
- hyperinsulinemia provokes increases in brain inflammation & beta amyloid[11]
- increased astrocyte nicotinic receptor alpha7 in hippocampus & entorhinal cortex associated with inflammatory mechanisms
- TNF-alpha upregulation may hasten cognitive decline[15]
- TNF-alpha is produced by glia, neurons
- TNF-alpha regulates synaptic communication
- effect in the hippocampus[15]
- higher plasma levels of IL-12 p70 in cognitively intact older adults associated with
- less cognitive decline in persons with significant burden of beta-amyloid
- fewer neurofibrillary tangles[31]
- higher plasma levels of IFN-gamma in cognitively intact older adults associated with slower cognitive decline independent of beta-amyloid burden[31]
- CD33 may be a microglial on-off switch, activating microglia as part of an inflammatory pathway sensing brain injury as an infection[39]
- microglia may mistake early Alzheimer's disease as an infection[39]
- progression of AD in the middle temporal gyrus occurs in 2 phases
- an early phase with a slow increase in pathology
- presence of inflammatory microglia & reactive astrocytes
- a loss of somatostatin-positive inhibitory neurons
- a remyelination response by oligodendrocyte precursors
- a later phase
- an early phase with a slow increase in pathology
- activation of the complement system
- generation of reactive oxygen species (hypothesis)
- 24-OH cholesterol
- membrane turnover
- upregulation of apolipoprotein E & other genes
- toxicity attenuated by peroxisome proliferators[6]
- up-regulation of redox-modulated transcription factors[7]
- alleles of apo E allegedly have different antioxidant capabilities in the order of E2 > E3 > E4[9]
- oxidation of UCHL1 Met & Cys
- UCHL1 found associated with neurofibrillary tangles
- MAO-B activity increases with ages & is further increased in AD, possibly increasing reactive oxygen species[14]
- diminished expression of REST in prefrontal cortex of patients with mild cognitive impairment or AD[20]
- 24-OH cholesterol
- neurotransmitter deficits occur secondary to neuronal injury
- neurons may enter cell cycle arresting in G2 phase prior tocell death[10]
- humanin may inhibit neurofibrillary pathology, toxicity of beta-amyloid, interactions of APP, neuronal apoptosis
- ECE2 may limit beta-amyloid peptide accumulation in brain & is down-regulated in inferior parietal lobe of patients with Alzheimer disease (at protein level)
- other molecules implicated in pathology of AD
- retromer complex
- CAT53/PNUTS
- nicotinic acetylcholine receptor
- NDRG2
- ubiquitin C-terminal hydrolases (?)
- ADAMTS4
- higher plasma leptin associated with lower risk of AD[16]
- neurogranin (absence of in dendrites)
- BPTF (FALZ) re-expression of fetal protein
- HERPUD1 interacts with PSEN1 & PSEN2 & is present in activated microglia in senile plaques (normally expression in the brain is restricted to neurons & vascular smooth muscle cells)
- UBXN4 accumulates in Alzheimer disease-afflicted brains
- over expression of C20orf203 (human-specific protein?)
- clusterin may play neuroprotective role[17]
- enhanced expression of REG1A-related transcripts & intraneuronal accumulation of REG1A-like proteins
- loss-of-function mutation in ABCA1 (present in 1:500 individuals)[24]
- RBFOX1 localizes around amyloid plaques & reduced expression of RBFOX1 correlates with higher amyloid-beta burden & greater cognitive impairment in preclinical & early Alzheimer's disease[27]
- rare coding variant in ABI3 is associated with late-onset Alzheimer's disease
- deletion of ABI3 significantly increases beta-amyloid plaques, & decreases microglia clustering around the amyloid plaques[37]
- alpha-endosulfine expression is increased in patients with Alzheimer's disease (see Comparative biology section)[38]
- misfolded proteins including TDP43, amyloid-beta, PHF-tau, & alpha-synuclein appear associated with cognitive impairment that typically progresses to severe dementia[28]
- epigenetically regulated MGMT expression may be involved in pathogenesis of AD, especially in women[41]
- proteins implicated in Alzheimer's disease may be found by analysis of proteome from brain, CSF & plasma[32]
- induced pluripotent stem cells (iPSC)
- induced from fibroblasts, processed into neurons
- iPSC neurons from familial AD or sporadic AD patients
- secrete more beta-amyloid[1-40] than controls
- contain more active GSK3B than controls
- contain higher phospho-tau/tau ratio than controls
- APP beta-secretase reversed these differences[18]
- changes in blood-based metabolites involved in energy metabolism occur 10 years before diagnosis of Alzheimer's disease[33]
- low levels of branched-chain amino acids & omega-3 fatty acids
- high levels of glucose, citrate, acetone, beta-hydroxybutyrate, & acetate
- higher fasting serum glucose levels are associated with lower regional cerebral metabolic rates for glucose in brain regions associated with AD (precuneus/ posterior cingulate, parietal cortex, prefrontal cortex, & occipital cortex)[19]
- blood-based biomarkers of Alzheimer's disease* show different dynamics of change after cardiac arrest[42]
- an increase of plasma p-tau 24 hours after cardiac arrest suggests ischemic brain injury may release p-tau from interstitial fluid & CSF vs chronic neuronal injury resulting in increases in plasma NfL & plasma total-tau
- delyed increases in plasma beta-amyloid after cardiac arrest suggest activation of amyloid processing in response to ischemia
- chronic mild cerebral ischemia may play a role in Alzheimer's disease[42] via associations between cerebral blood flow, vascular health, & tau pathology driven in part by beta-amyloid burden[29]
* see laboratory evaluation of Alzheimer's disease
Comparative biology
- in mice genetically engineered to produce large amounts of microtubule-associate protein tau, mice that produced apoE4 developed markedly more deposits of tau, greater brain atrophy, & greater brain inflammation than did mice that made apoE2 or apoE3; mice that made no apoE protein were protected
- inflammatory cytokines produced by microglia from apoE4 producing mice implicated
- dynamin-1-like protein may play a role in NLRP3 inflammasome activation via inhibition of hexokinase-1 & glycolysis resulting in oligodendrocyte degeneration & white matter changes in mice[30]
- alpha-endosulfine is an endogenous ligand of the ATP-sensitive K+ channel in mice & negatively regulates neprilysin-catalyzed proteolytic degradation of beta-amyloid; expression is increased in mouse models for Alzheimer's disease & in patients with Alzheimer's disease[38]
More general terms
More specific terms
Additional terms
- A4 amyloid peptide; beta-peptide
- amyloid precursor protein; A4/beta amyloid precursor protein (APP)
- apolipoprotein E (APOE)
- microtubule-associated protein tau (neurofibrillary tangle protein, paired helical filament-tau, PHF-tau, MAPT, MTBT1, m-tau, mtau)
- oxysterol; hydroxysterol
- pathologic mechanisms in Alzheimer's disease
- presenilin-1; PS-1; EC=3.4.23.-; protein S182; contains: presenilin-1 NTF subunit; contains: presenilin-1 CTF subunit; contains: presenilin-1 CTF12; PS1-CTF12 (PSEN1, AD3, PS1, PSNL1)
- presenilin-2; PS-2; STM-2; E5-1; AD3LP; AD5; contains: presenilin-2 NTF subunit; contains: presenilin-2 CTF subunit (PSEN2, AD4, PS2, PSNL2, STM2)
References
- ↑ 1.0 1.1 Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
- ↑ 2.0 2.1 Tacnet-Delorme P, Chevallier S, Arlaud GJ. Beta-amyloid fibrils activate the C1 complex of complement under physiological conditions: evidence for a binding site for A beta on the C1q globular regions. J Immunol. 2001 Dec 1;167(11):6374-81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11714802
- ↑ 3.0 3.1 Bergamaschini L, Donarini C, Gobbo G, Parnetti L, Gallai V. Activation of complement and contact system in Alzheimer's disease. Mech Ageing Dev. 2001 Nov;122(16):1971-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11589915
- ↑ 4.0 4.1 Shen Y, Lue L, Yang L, Roher A, Kuo Y, Strohmeyer R, Goux WJ, Lee V, Johnson GV, Webster SD, Cooper NR, Bradt B, Rogers J. Complement activation by neurofibrillary tangles in Alzheimer's disease. Neurosci Lett. 2001 Jun 15;305(3):165-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11403931
- ↑ 5.0 5.1 McGeer PL, McGeer EG, Yasojima K. Alzheimer disease and neuroinflammation. J Neural Transm Suppl. 2000;59:53-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10961418
- ↑ 6.0 6.1 Inestrosa NC, Godoy JA, Quintanilla RA, Koenig CS, Bronfman M. Peroxisome proliferator-activated receptor gamma is expressed in hippocampal neurons and its activation prevents beta- amyloid neurodegeneration: role of Wnt signaling. Exp Cell Res. 2005 Mar 10;304(1):91-104. Epub 2004 Dec 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15707577
Camacho IE, Serneels L, Spittaels K, Merchiers P, Dominguez D, De Strooper B. Peroxisome-proliferator-activated receptor gamma induces a clearance mechanism for the amyloid-beta peptide. J Neurosci. 2004 Dec 1;24(48):10908-17. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15574741 - ↑ 7.0 7.1 Lavrovsky Y, Chatterjee B, Clark RA, Roy AK. Role of redox-regulated transcription factors in inflammation, aging and age-related diseases. Exp Gerontol. 2000 Aug;35(5):521-32. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10978675
- ↑ 8.0 8.1 Yamaguchi H, Sugihara S, Ogawa A, Oshima N, Ihara Y. Alzheimer beta amyloid deposition enhanced by apoE epsilon4 gene precedes neurofibrillary pathology in the frontal association cortex of nondemented senior subjects. J Neuropathol Exp Neurol. 2001 Jul;60(7):731-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11444802
- ↑ 9.0 9.1 Lauderback CM, Kanski J, Hackett JM, Maeda N, Kindy MS, Butterfield DA. Apolipoprotein E modulates Alzheimer's Abeta(1-42)-induced oxidative damage to synaptosomes in an allele-specific manner. Brain Res. 2002 Jan 4;924(1):90-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11743999
- ↑ 10.0 10.1 Yang Y, Geldmacher DS, Herrup K. DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci. 2001 Apr 15;21(8):2661-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11306619
- ↑ 11.0 11.1 Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, Cook DG, Peskind ER, Baker LD, Goldgaber D, Nie W, Asthana S, Plymate SR, Schwartz MW, Craft S. Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Arch Neurol. 2005 Oct;62(10):1539-44. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/16216936 <Internet> http://archneur.ama-assn.org/cgi/content/short/62/10/1539
- ↑ 12.0 12.1 Small SA, Kent K, Pierce A, Leung C, Kang MS, Okada H, Honig L, Vonsattel JP, Kim TW. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Ann Neurol. 2005 Dec;58(6):909-19. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16315276
- ↑ 13.0 13.1 Lauren J et al. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-oligomers. Nature 2009 Feb 26; 457:1128 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19242475
Cisse M and Mucke L. Alzheimer's disease: A prion protein connection. Nature 2009 Feb 26; 457:1090. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19242462 - ↑ 14.0 14.1 Hirvonen J et al. Assessment of MAO-B occupancy in the brain with PET and [11C]-L-deprenyl-D2: A dose-finding study with a novel MAO-B inhibitor, EVT 301. Clin Pharmacol Ther 2009 May; 85:506. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19129751
- ↑ 15.0 15.1 15.2 Journal Watch, Sept 8, 2009 Holmes C et al Systemic inflammation and disease progression in Alzheimer disease Neurology 2009 73:768-774 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19738171
Torro J Is Etanercept Safe and Well Tolerated in Alzheimer Disease? NEJM Journal Watch. May 27, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Butchart J et al. Etanercept in Alzheimer disease: A randomized, placebo- controlled, double-blind, phase 2 trial. Neurology 2015 May 26; 84:2161 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25934853 <Internet> http://www.neurology.org/content/84/21/2161 - ↑ 16.0 16.1 Lieb W et al. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. JAMA 2009 Dec 16; 302:2565. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20009056
- ↑ 17.0 17.1 Schrijvers EMC et al. Plasma clusterin and the risk of Alzheimer disease. JAMA 2011 Apr 6; 305:1322. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21467285
- ↑ 18.0 18.1 Israel MA et al. Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature 2012 Jan 25; PMID: https://www.ncbi.nlm.nih.gov/pubmed/22278060
- ↑ 19.0 19.1 Burns CM et al. Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions. Neurology 2013 Apr 23; 80:1557. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23535495 <Internet> http://www.neurology.org/content/80/17/1557
- ↑ 20.0 20.1 Lu T, Aron L, Zullo J et al REST and stress resistance in ageing and Alzheimer's disease. Nature. March 19, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24670762 <Internet> http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13163.html
Tsai LH and Madabhushi R Alzheimer's disease: A protective factor for the ageing brain. Nature. March 19, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24670758 <Internet> http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13214.html - ↑ 21.0 21.1 21.2 Bloom GS Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 2014 Apr;71(4):505-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24493463
- ↑ 22.0 22.1 Justice NJ et al. Posttraumatic stress disorder-like induction elevates beta- amyloid levels, which directly activates corticotropin- releasing factor neurons to exacerbate stress responses. J Neurosci 2015 Feb 11; 35:2612 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25673853 <Internet> http://www.jneurosci.org/content/35/6/2612
- ↑ 23.0 23.1 Wang L et al. Evaluation of tau imaging in staging Alzheimer disease and revealing interactions between beta-amyloid and tauopathy. JAMA Neurol 2016 Jul 25 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27454922 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2537339
- ↑ 24.0 24.1 Nordestgaard LT, Tybjaerg-Hansen A, Nordestgaard BG et al Loss-of-function mutation in ABCA1 and risk of Alzheimer's disease and cerebrovascular disease. Alzheimers Dement. 2015 Dec;11(12):1430-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26079414
- ↑ Shi Y, Yamada K, Liddelow SA et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 2017 Sep 28; 549:523. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28959956
- ↑ 26.0 26.1 George J. Do Amyloid Plaques Drive Tau Deposition? New study ties tau production to amyloid burden. MedPage Today. March 21, 2018 https://www.medpagetoday.com/neurology/alzheimersdisease/71910
Sato C, Barthelemy NR, Mawuenyega KG Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 97(6):1284-1298. March 21, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29566794 <Internet> http://www.cell.com/neuron/fulltext/S0896-6273(18)30136-3 - ↑ 27.0 27.1 Raghavan NS, Dumitrescu L, Mormino E et al Association Between Common Variants in RBFOX1, an RNA-Binding Protein, and Brain Amyloidosis in Early and Preclinical Alzheimer Disease. JAMA Neurol. Published online June 22, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32568366 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2767374
- ↑ 28.0 28.1 Karanth S, Nelson PT, Katsumata Y et al Prevalence and Clinical Phenotype of Quadruple Misfolded Proteins in Older Adults. JAMA Neurol. Published online June 22, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32568358 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2767373
- ↑ 29.0 29.1 Albrecht d ET AL Associations between vascular function and tau PET are associated with global cognition and amyloid. J Neuroscience 2020 Oct 12;JN-RM-1230-20 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33046556 https://www.jneurosci.org/content/early/2020/10/09/JNEUROSCI.1230-20.2020
- ↑ 30.0 30.1 Zhang X, Wang R, Hu D et al Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer's disease. Science Advances 2020. Vol. 6, no. 49, eabb8680. Dec 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33277246 PMCID: PMC7717916 Free PMC article https://advances.sciencemag.org/content/6/49/eabb8680
- ↑ 31.0 31.1 31.2 George J Two Inflammatory Proteins Linked With Slower Cognitive Decline. Surprise finding ties plasma cytokine levels with Alzheimer's biomarkers and cognition. MedPage Today June 23, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/93257
Yang HS, Zhang C, Carlyle BC et al Plasma IL-12/IFN-gamma axis predicts cognitive trajectories in cognitively unimpaired older adults. Alzheimer's & Dementia. 2021. June 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34160128 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12399 - ↑ 32.0 32.1 Yang C, Farias FHG, Ibanez L et al Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders. Nat Neurosci 2021. July 8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34239129 https://www.nature.com/articles/s41593-021-00886-6
- ↑ 33.0 33.1 Anderson P Changes in Metabolism Tied to Risk of Subsequent Dementia. Medscape. July 29, 2021 https://www.medscape.com/viewarticle/955575
Alzheimer's Association International Conference AAIC 2021. Session: Genome, Gut Microbiome, and Metabolome Jointly Inform Alzheimer's Disease. Presented July 26, 2021. - ↑ 34.0 34.1 Pascoal TA, Benedet AL, Ashton NJ et al. Microglial activation and tau propagate jointly across Braak stages. Nat Med 2021. August 21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34446931 https://www.nature.com/articles/s41591-021-01456-w
- ↑ Jonsson T et al Variant of TREM2 Associated with the Risk of Alzheimer's Disease N Engl J Med. November 14, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23150908 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1211103
Guerreiro R et al TREM2 Variants in Alzheimer's Disease N Engl J Med. November 14, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23150934 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1211851 - ↑ 36.0 36.1 Hubbard EE, Heil LR, Merrihew GE et al Does Data-Independent Acquisition Data Contain Hidden Gems? A Case Study Related to Alzheimer's Disease. J. Proteome Res. 2021, Nov 24 https://pubs.acs.org/doi/10.1021/acs.jproteome.1c00558
- ↑ 37.0 37.1 Mobley I New research finds ABI3 gene function in Alzheimer's disease. Front Line Genomics. Nov 8, 2021 https://frontlinegenomics.com/new-research-finds-abi3-gene-function-in-alzheimers-disease/
- ↑ 38.0 38.1 38.2 Watamura N, Kakiya N, Nilsson P et al Somatostatin-evoked Abeta catabolism in the brain: Mechanistic involvement of alpha-endosulfine-KATP channel pathway. Mol Psychiatry 2021. Nov 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34737456 https://www.nature.com/articles/s41380-021-01368-8
- ↑ 39.0 39.1 39.2 Stetka B The Cell That Might Trigger Alzheimer's Disease. Medscape. Jan 31, 2022 https://www.medscape.com/viewarticle/967592
- ↑ 40.0 40.1 40.2 Elliott Knapp D Novel Biomarker Found for Alzheimer's Disease. Medscape. January 20, 2022 https://www.medscape.com/viewarticle/966918
Zaretsky DV, Zaretskaia MV, Molkov YI et al Patients with Alzheimer's disease have increased cellular amyloid uptake. medRxiv 2022. Jan 13 https://www.medrxiv.org/content/10.1101/2022.01.12.22269196v1.full - ↑ 41.0 41.1 Chung J, Das A, Sun X et al Genome-wide association and multi-omics studies identify MGMT as a novel risk gene for Alzheimer's disease among women. Alzheimers & Dementia, 2022. June 30 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35770850 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12719
- ↑ 42.0 42.1 42.2 Ashton NJ, Moseby-Knappe M, Benedet AL et al Alzheimer Disease Blood Biomarkers in Patients With Out-of-Hospital Cardiac Arrest. JAMA Neurol. Published online March 6, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36877496 PMCID: PMC9989959 Free PMC article. https://jamanetwork.com/journals/jamaneurology/fullarticle/2802181
- ↑ 43.0 43.1 Taddei RN, Perbet R, Mate de Gerando A et al Tau Oligomer-Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease. JAMA Neurol. Published online October 9, 2023. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37812432 https://jamanetwork.com/journals/jamaneurology/fullarticle/2809939
- ↑ 44.0 44.1 Gabitto MI, Travaglini KJ, Rachleff VM et al Integrated multimodal cell atlas of Alzheimer's disease Nat Neurosci. 2024 Oct 14. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39402379 https://www.nature.com/articles/s41593-024-01774-5