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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Neurosteroids as regenerative agents in the brain: therapeutic implications
TL;DR: Allopregnanolone serves as proof of concept for therapeutics that target endogenous regeneration, windows of therapeutic opportunity for regeneration, and critical system biology factors that will determine the efficacy of regeneration.
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Depressive Symptoms in Mild Cognitive Impairment Predict Greater Atrophy in Alzheimer’s Disease-Related Regions
Grace J. Lee,Po H. Lu,Xue Hua,Suh Lee,Stephanie Wu,Ken Nguyen,Edmond Teng,Alex D. Leow,Alex D. Leow,Clifford R. Jack,Arthur W. Toga,Michael W. Weiner,George Bartzokis,Paul M. Thompson +13 more
TL;DR: Depressive symptoms in individuals with MCI were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD.
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Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease
Douglas C. Dean,Samuel A. Hurley,Steven Kecskemeti,J. Patrick O’Grady,Cristybelle Canda,Nancy J. Davenport-Sis,Cynthia M. Carlsson,Henrik Zetterberg,Henrik Zetterberg,Kaj Blennow,Sanjay Asthana,Mark A. Sager,Sterling C. Johnson,Andrew L. Alexander,Barbara B. Bendlin +14 more
TL;DR: Findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process, as well as clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials.
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Neuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments
TL;DR: It is suggested that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair.
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Unbiased tensor-based morphometry: improved robustness and sample size estimates for Alzheimer's disease clinical trials.
Xue Hua,Derrek P. Hibar,Christopher R.K. Ching,Christina P. Boyle,Priya Rajagopalan,Boris A. Gutman,Alex D. Leow,Arthur W. Toga,Clifford R. Jack,Danielle J Harvey,Michael W. Weiner,Paul M. Thompson +11 more
TL;DR: TBM is an unbiased, robust, high-throughput imaging surrogate marker for large, multi-site neuroimaging studies and clinical trials of AD and MCI and shows how selective data exclusion affects sample size estimates, motivating an objective comparison of different analysis techniques based on statistical power and robustness.
References
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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.