Alzheimer's disease as homeostatic responses to age-related myelin breakdown
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TLDR
This work delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides "upstream" treatment targets and reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits as by-products of homeostatic myelin repair processes.Citations
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Prion Protein Interactome: Identifying Novel Targets in Slowly and Rapidly Progressive Forms of Alzheimer's Disease.
Saima Zafar,Mohsin Shafiq,Neelam Younas,Matthias Schmitz,Isidre Ferrer,Isidre Ferrer,Inga Zerr +6 more
TL;DR: The data suggest distinct PrP involvement in association with the altered PrP interacting protein in rpAD, though the pathophysiological significance of these interactions remains to be established.
Subjects harboring presenilin familial Alzheimer's disease mutations exhibit diverse white matter biochemistry alterations.
Alex E. Roher,Chera L. Maarouf,Michael Malek-Ahmadi,Jeffrey R. Wilson,Tyler A. Kokjohn,Ian D. Daugs,Charisse M. Whiteside,Walter M. Kalback,Mi Mi P. Macias,Sandra A. Jacobson,Marwan N. Sabbagh,Bernardino Ghetti,Thomas G. Beach +12 more
TL;DR: In this article, the white matter (WM) represents about 50% of the cerebrum and this area of the brain is substantially atrophied and profoundly abnormal in both sporadic AD (SAD) and familial AD (FAD).
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Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum.
Nikki H. Stricker,David H. Salat,Taylor Kuhn,Jessica M. Foley,Jenessa S. Price,Lars T. Westlye,Michael Esterman,Regina E. McGlinchey,William P. Milberg,Elizabeth C. Leritz +9 more
TL;DR: Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC.
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Perspectives in Molecular Imaging Using Staging Biomarkers and Immunotherapies in Alzheimer’s Disease
TL;DR: Early diagnosis is the challenge task that needs to look first at plausible mechanisms of actions behind therapies, and combining them would allow for the development of efficient AD treatment in a near future.
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Elevated Insulin and Insulin Resistance are Associated with Altered Myelin in Cognitively Unimpaired Middle-Aged Adults.
J. Patrick O’Grady,Douglas C. Dean,Kao Lee Yang,Cristybelle‐Marie Canda,Siobhan M. Hoscheidt,Erika J. Starks,Andrew P. Merluzzi,Samuel A. Hurley,Nancy J. Davenport,Ozioma C. Okonkwo,Rozalyn M. Anderson,Sanjay Asthana,Sterling C. Johnson,Andrew L. Alexander,Barbara B. Bendlin +14 more
TL;DR: The relationships between insulin, IR, and myelin were examined, with the hypothesis that IR would be associated with reduced myelin.
References
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Journal ArticleDOI
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
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Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
Robert D. Terry,Eliezer Masliah,David P. Salmon,Nelson Butters,Richard DeTeresa,Robert Hill,Lawrence A. Hansen,Robert Katzman +7 more
TL;DR: Both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of patients with Alzheimer's disease and 9 neuropathologically normal subjects reveal very powerful correlations with all three psychological assays.
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Alzheimer's Disease Is a Synaptic Failure
TL;DR: Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid β protein.
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Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory.
Ganesh M. Shankar,Shaomin Li,Tapan Mehta,Amaya Garcia-Munoz,Nina E. Shepardson,Imelda M. Smith,Francesca Brett,Michael A. Farrell,Michael J. Rowan,Cynthia A. Lemere,Ciaran M. Regan,Dominic M. Walsh,Bernardo L. Sabatini,Dennis J. Selkoe +13 more
TL;DR: It is concluded that soluble Aβ oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.