Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre
Jon B. Toledo,Steven E. Arnold,Kevin M. Raible,Johannes Brettschneider,Sharon X. Xie,Murray Grossman,Sarah E. Monsell,Walter A. Kukull,John Q. Trojanowski +8 more
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TLDR
Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in Alzheimer's disease than in other neurodegenerative disorders, especially in younger subjects, and lowers the threshold for dementia due to Alzheimer’s disease and α-synucleinopathies, which suggests that these disorders should be targeted by treatments for cerebroVascular disease.Abstract:
Cerebrovascular disease and vascular risk factors are associated with Alzheimer’s disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity. Presence of cerebrovascular disease, vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer’s Coordinating Centre database with a single neurodegenerative disease diagnosis (Alzheimer’s disease, frontotemporal lobar degeneration due to tau, and TAR DNA-binding protein 43 immunoreactive deposits, α-synucleinopathies, hippocampal sclerosis and prion disease) based on a neuropathological examination with or without cerebrovascular disease, defined neuropathologically. In addition, 210 ‘unremarkable brain’ cases without cognitive impairment, and 280 cases with pure cerebrovascular disease were included for comparison. Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis. After controlling for age and gender as fixed effects and centre as a random effect, we observed that α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease showed a lower prevalence of coincident cerebrovascular disease than patients with Alzheimer’s disease, and this was more significant in younger subjects. When cerebrovascular disease was also present, patients with Alzheimer’s disease and patients with α-synucleinopathy showed relatively lower burdens of their respective lesions than those without cerebrovascular disease in the context of comparable severity of dementia at time of death. Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in Alzheimer’s disease than in other neurodegenerative disorders, especially in younger subjects, and lowers the threshold for dementia due to Alzheimer’s disease and α-synucleinopathies, which suggests that these disorders should be targeted by treatments for cerebrovascular disease.read more
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Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: A potential therapeutic molecule for Alzheimer's disease.
TL;DR: Melatonin shows a potent neuroprotective effect and can prevent or slow down the progression of AD, supporting the view that melatonin is a potential therapeutic molecule for AD.
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Deep ensemble learning for Alzheimer's disease classification.
TL;DR: Wang et al. as mentioned in this paper presented a deep ensemble learning framework that aims to harness deep learning algorithms to integrate multisource data and tap the "wisdom of experts", where two sparse autoencoders are trained for feature learning to reduce the correlation of attributes and diversify the base classifiers ultimately.
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Alzheimer's Disease: The Link Between Amyloid-β and Neurovascular Dysfunction.
TL;DR: AD vascular disturbances as they relate to Aβ are described, including chronic cerebral hypoperfusion, hypertension, altered neurovascular coupling, and deterioration of the blood-brain barrier.
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Causal Associations Between Modifiable Risk Factors and the Alzheimer's Phenome.
TL;DR: The purpose of this study was to infer causal relationships between 22 previously reported risk factors for Alzheimer's disease and the “AD phenome”: AD, AD age of onset (AAOS), hippocampal volume, cortical surface area and thickness, cerebrospinal fluid levels of amyloid‐β, tau, and ptau181.
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Translational models for vascular cognitive impairment: a review including larger species
Atticus H. Hainsworth,Atticus H. Hainsworth,Stuart M. Allan,Johannes Boltze,Johannes Boltze,Catriona J Cunningham,Chad Farris,Elizabeth Head,Masafumi Ihara,Jeremy D. Isaacs,Jeremy D. Isaacs,Raj N. Kalaria,Saskia A J Lesnik Oberstein,Mark B. Moss,Björn Nitzsche,Björn Nitzsche,Gary A. Rosenberg,Julie W. Rutten,Melita Salkovic-Petrisic,Aron M. Troen +19 more
TL;DR: It is concluded that translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; rodent models of VCI are limited by paucity of white matter; and further translational Models, and improved cognitive testing instruments, are required.
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