Decreased Cortical FADD Protein is Associated with Clinical Dementia and Cognitive Decline in an Elderly Community Sample

Overview

Journal Mol Neurodegener

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2017 Mar 22

PMID 28320441

Citations 10

Authors

Alfredo Ramos-Miguel

Jesus A Garcia-Sevilla

Alasdair M Barr

Thomas A Bayer

Peter Falkai

Sue E Leurgans

Julie A Schneider

David A Bennett

William G Honer

M Julia Garcia-Fuster

Affiliations

Soon will be listed here.

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.

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