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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The connectomics of brain disorders
TL;DR: This work considers how brain-network topology shapes neural responses to damage, highlighting key maladaptive processes and the resources and processes that enable adaptation, and shows how knowledge of network topology allows for predictive models of the spread and functional consequences of brain disease.
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The Cellular Phase of Alzheimer’s Disease
TL;DR: Evidence supporting a long, complex cellular phase consisting of feedback and feedforward responses of astrocytes, microglia, and vasculature is reviewed.
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Intramuscular desferrioxamine in patients with Alzheimer's disease
TL;DR: In this paper, a single-blind study was conducted to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine.
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White matter characterization with diffusional kurtosis imaging.
TL;DR: A physically meaningful interpretation of DKI metrics in white matter regions consisting of more or less parallel aligned fiber bundles is provided by modeling the tissue as two non-exchanging compartments, the intra-axonal space and extra-AXonal space.
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Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease.
Wei Ting Chen,Wei Ting Chen,Ashley Lu,Ashley Lu,Katleen Craessaerts,Katleen Craessaerts,Benjamin Pavie,Carlo Sala Frigerio,Carlo Sala Frigerio,Carlo Sala Frigerio,Nikky Corthout,Xiaoyan Qian,Jana Lalakova,Malte Kühnemund,Iryna Voytyuk,Iryna Voytyuk,Leen Wolfs,Leen Wolfs,Renzo Mancuso,Renzo Mancuso,Evgenia Salta,Evgenia Salta,Sriram Balusu,Sriram Balusu,An Snellinx,An Snellinx,Sebastian Munck,Aleksandra Jurek,José Fernández Navarro,Takaomi C. Saido,Inge Huitinga,Inge Huitinga,Joakim Lundeberg,Mark Fiers,Mark Fiers,Mark Fiers,Bart De Strooper,Bart De Strooper,Bart De Strooper +38 more
TL;DR: Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
References
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Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer's disease.
TL;DR: It is reported that stress-level glucocorticoid administration increases Aβ formation by increasing steady-state levels of amyloid precursor protein (APP) and β-APP cleaving enzyme and augments tau accumulation, indicating that this hormone also accelerates the development of neurofibrillary tangles.
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Marked loss of myelinated nerve fibers in the human brain with age.
TL;DR: The fiber diameter distribution showed that primarily the thinner fibers were lost with a relative preservation of the thicker ones, and the marked loss of myelinated nerve fibers with age could explain some of the cognitive decline seen in the elderly.
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BACE1, a Major Determinant of Selective Vulnerability of the Brain to Amyloid-β Amyloidogenesis, is Essential for Cognitive, Emotional, and Synaptic Functions
Fiona M. Laird,Huaibin Cai,Alena Savonenko,Mohamed H. Farah,Kaiwen He,Tatyana Melnikova,Hongjin Wen,Hsueh Cheng Chiang,Guilian Xu,Guilian Xu,Vassilis E. Koliatsos,David R. Borchelt,David R. Borchelt,Donald L. Price,Hey Kyoung Lee,Philip C. Wong +15 more
TL;DR: It is demonstrated that BACE1, enriched in neurons of the CNS, is a major determinant that predisposes the brain to Aβ amyloidogenesis, and future studies should be alert to potential mechanism-based side effects that may occur with BACE2 and α-secretase anti-amyloidogenic activities in neurons.
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Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches.
TL;DR: Fibrillar amyloid deposition is more detrimental to neuronal circuitry than previously thought, underscoring the importance of prevention and early clearance of plaques.
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Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia.
Beng-Choon Ho,Nancy C. Andreasen,Peg Nopoulos,Stephan Arndt,Vincent A. Magnotta,Michael Flaum +5 more
TL;DR: There are ongoing changes in the brains of schizophrenic patients during the initial years after diagnosis despite ongoing antipsychotic drug treatment, and progressive changes seem to be most evident in the frontal lobes and to correlate with functional impairment.