Open Collections

UBC Faculty Research and Publications

Decreased cortical FADD protein is associated with clinical dementia and cognitive decline in an elderly community sample Ramos-Miguel, Alfredo; García-Sevilla, Jesús A; Barr, Alasdair M.; Bayer, Thomas A.; Falkai, Peter; Leurgans, Sue E.; Schneider, Julie A.; Bennett, David A.; Honer, William G. (William George), 1957-; García-Fuster, M. J.

Abstract

Background: FADD (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-FADD). This study investigated the possible association of FADD forms with age-related neuropathologies, cognitive function, and the odds of dementia in an elderly community sample. Methods FADD forms were quantified by western blot analysis in dorsolateral prefrontal cortex (DLPFC) samples from a large cohort of participants in a community-based aging study (Memory and Aging Project, MAP), experiencing no-(NCI, n = 51) or mild-(MCI, n = 42) cognitive impairment, or dementia (n = 57). Results Cortical FADD was lower in subjects with dementia and lower FADD was associated with a greater load of amyloid-β pathology, fewer presynaptic terminal markers, poorer cognitive function and increased odds of dementia. Together with the observations of FADD redistribution into tangles and dystrophic neurites within plaques in Alzheimer’s disease brains, and its reduction in APP23 mouse cortex, the results suggest this multifunctional protein might participate in the mechanisms linking amyloid and tau pathologies during the course of the illness. Conclusions The present data suggests FADD as a putative biomarker for pathological processes associated with the course of clinical dementia.

Item Metadata

Title
Decreased cortical FADD protein is associated with clinical dementia and cognitive decline in an elderly community sample
Creator
Ramos-Miguel, Alfredo; García-Sevilla, Jesús A; Barr, Alasdair M.; Bayer, Thomas A.; Falkai, Peter; Leurgans, Sue E.; Schneider, Julie A.; Bennett, David A.; Honer, William G. (William George), 1957-; García-Fuster, M. J.
Publisher
BioMed Central
Date Issued
2017-03-20
Description
Background: FADD (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-FADD). This study investigated the possible association of FADD forms with age-related neuropathologies, cognitive function, and the odds of dementia in an elderly community sample. Methods FADD forms were quantified by western blot analysis in dorsolateral prefrontal cortex (DLPFC) samples from a large cohort of participants in a community-based aging study (Memory and Aging Project, MAP), experiencing no-(NCI, n = 51) or mild-(MCI, n = 42) cognitive impairment, or dementia (n = 57). Results Cortical FADD was lower in subjects with dementia and lower FADD was associated with a greater load of amyloid-β pathology, fewer presynaptic terminal markers, poorer cognitive function and increased odds of dementia. Together with the observations of FADD redistribution into tangles and dystrophic neurites within plaques in Alzheimer’s disease brains, and its reduction in APP23 mouse cortex, the results suggest this multifunctional protein might participate in the mechanisms linking amyloid and tau pathologies during the course of the illness. Conclusions The present data suggests FADD as a putative biomarker for pathological processes associated with the course of clinical dementia.
Subject
Alzheimer's disease; Aging; Neurotoxicity; Neuroplasticity; Apoptosis
Genre
Article
Type
Text
Language
eng
Date Available
2017-03-20
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0343277
URI
http://hdl.handle.net/2429/60951
Affiliation
Medicine, Faculty of; Non UBC; Anesthesiology, Pharmacology and Therapeutics, Department of; Psychiatry, Department of
Citation
Molecular Neurodegeneration. 2017 Mar 20;12(1):26
Publisher DOI
10.1186/s13024-017-0168-x
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
Aggregated Source Repository
DSpace

Item Media

Item Citations and Data

Rights

Attribution 4.0 International (CC BY 4.0)