Decreased cortical FADD protein is associated with clinical dementia and cognitive decline in an elderly community sample
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, cog...
| Authors: | , , , , , , , , , |
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| Format: | article |
| Publication Date: | 2017 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/20419 |
| Online Access: | http://hdl.handle.net/20.500.12105/20419 |
| Access Level: | Open access |
| Keyword: | Alzheimer's disease Aging Neurotoxicity Neuroplasticity Apoptosis Animales Biomarcadores Femenino Masculino Disfunción Cognitiva Técnica del Anticuerpo Fluorescente Humanos Ratones Transgénicos Anciano de 80 o más Años Ratones Corteza Prefrontal Western Blotting Proteína de Dominio de Muerte Asociada a Fas |
| Summary: | 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-beta 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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