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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Journal ArticleDOI
Monosialotetrahexosylganglioside Promotes Early Aβ42 Oligomer Formation and Maintenance.
Dong Yan Zhang,Jian Wang,Rebecca Fleeman,Madison K. Kuhn,Matthew T. Swulius,Elizabeth A. Proctor,Nikolay V. Dokholyan +6 more
TL;DR: It is demonstrated that GM1 is a critical trigger of Aβ oligomerization and aggregation, and the roles of GM1 in mediating early A β oligomer formation and maintenance are uncovered, providing a novel direction for pharmaceutical research for AD.
Development of MALDI Mass Spectrometry Imaging Methods for Probing Spatial Lipid Biochemistry of Amyloid Plaques in Alzheimer's Disease
TL;DR: Lipids are important components of amyloid plaques and above mentioned novel MALDI-MSI methods in combination with other modalities have great potential for probing spatial lipid molecular pathology ofAmyloid Plaques which can provide novel insights into AD pathogenesis.
Journal ArticleDOI
The Hidden Role of Non-Canonical Amyloid β Isoforms in Alzheimer’s Disease
TL;DR: In this article , a comprehensive overview of the contributions of these neglected Aβ variants to microglia activation is provided, including the impact of Aβ receptors, signaling cascades, scavenger mechanisms, and genetic variations on the physiological responses towards various Aβ species.
Book ChapterDOI
Membrane-Associated Diseases
TL;DR: Since almost all biological processes are at some level affected by membranes, it is difficult to select just a few representative examples of the many membrane-associated human afflictions.
Dissertation
Axonal and synaptic pathology in Alzheimer’s disease
TL;DR: This thesis further clarified the pathological role of Aβ plaques in mediating cytoskeletal dystrophic changes and specific synaptic loss and identified the novel finding of focal demyelination associated with Aβ deposits.
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.