Alzheimer's Disease and the Amyloid-β Peptide
M. Paul Murphy,Harry LeVine +1 more
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TLDR
Interestingly, deposited Abeta in AD is different from that found in animal models and does not show the same physical and biochemical characteristics as the amyloid found in AD, which raises important issues regarding the development and testing of future therapeutic agents.Abstract:
Alzheimer's disease (AD) pathogenesis is widely believed to be driven by the production and deposition of the amyloid-beta peptide (Abeta). For many years, investigators have been puzzled by the weak to nonexistent correlation between the amount of neuritic plaque pathology in the human brain and the degree of clinical dementia. Recent advances in our understanding of the development of amyloid pathology have helped solve this mystery. Substantial evidence now indicates that the solubility of Abeta, and the quantity of Abeta in different pools, may be more closely related to disease state. The composition of these pools of Abeta reflects different populations of amyloid deposits and has definite correlates with the clinical status of the patient. Imaging technologies, including new amyloid imaging agents based on the chemical structure of histologic dyes, are now making it possible to track amyloid pathology along with disease progression in the living patient. Interestingly, these approaches indicate that the Abeta deposited in AD is different from that found in animal models. In general, deposited Abeta is more easily cleared from the brain in animal models and does not show the same physical and biochemical characteristics as the amyloid found in AD. This raises important issues regarding the development and testing of future therapeutic agents.read more
Citations
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Inflammation as a central mechanism in Alzheimer's disease
Jefferson W. Kinney,Shane M. Bemiller,Andrew S. Murtishaw,Amanda M. Leisgang,Arnold Salazar,Bruce T. Lamb +5 more
TL;DR: An overview of inflammation in AD is provided and a detailed coverage of a number of microglia‐related signaling mechanisms that have been implicated in AD are reviewed.
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A new era for understanding amyloid structures and disease.
TL;DR: The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available and reveal cross-β structures that are far more intricate than anticipated.
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A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer's disease and its prodromal stages
TL;DR: The studies reviewed indicate that the classification frameworks formulated on the basis of these features show promise for individualized diagnosis and prediction of clinical progression, and a detailed account of AD classification challenges is provided.
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Amyloid β oligomers constrict human capillaries in Alzheimer’s disease via signaling to pericytes
Ross Nortley,Nils Korte,Pablo Izquierdo,Chanawee Hirunpattarasilp,Anusha Mishra,Zane Jaunmuktane,Vasiliki Kyrargyri,Thomas Pfeiffer,Lila Khennouf,Christian Madry,Hui Gong,Angela Richard-Loendt,Wenhui Huang,Takashi Saito,Takaomi C. Saido,Sebastian Brandner,Huma Sethi,David Attwell +17 more
TL;DR: The role of pericytes in Alzheimer’s disease is examined by examining cerebral capillaries in humans and mice developing AD, and by applying amyloid-β in the oligomeric form, which is thought to contribute to cognitive decline.
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Drug treatments in Alzheimer's disease.
TL;DR: Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials and results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution.
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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TL;DR: The shared 4-kDa subunit indicates a common origin for the amyloids of the plaque core and of the congophilic angiopathy of Alzheimer disease and Down syndrome.
Journal ArticleDOI
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Dominic M. Walsh,Igor Klyubin,Julia V. Fadeeva,William K. Cullen,Roger Anwyl,Michael S. Wolfe,Michael J. Rowan,Dennis J. Selkoe +7 more
TL;DR: It is reported that natural oligomers of human Aβ are formed soon after generation of the peptide within specific intracellular vesicles and are subsequently secreted from the cell, indicating that synaptotoxic Aβ oligomers can be targeted therapeutically.
Journal ArticleDOI
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