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...
| Autores: | , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Conselleria de Salut i Consum del Govern de les Illes Balears |
| Repositorio: | Docusalut |
| Idioma: | inglés |
| OAI Identifier: | oai:docusalut.com:20.500.13003/9901 |
| Acesso em linha: | https://hdl.handle.net/20.500.13003/9901 |
| Access Level: | acceso abierto |
| Palavra-chave: | Blotting, Western Mice Fas-Associated Death Domain Protein Animals Female Biomarkers Male Fluorescent Antibody Technique Mice, Transgenic Cognitive Dysfunction Humans Aged, 80 and over Prefrontal Cortex Anciano de 80 o más Años Ratones Transgénicos Corteza Prefrontal Disfunción Cognitiva Ratones Humanos Western Blotting Proteína de Dominio de Muerte Asociada a Fas Animales Biomarcadores Femenino Técnica del Anticuerpo Fluorescente Masculino Alzheimer's disease Aging Neurotoxicity Neuroplasticity Apoptosis |
| Resumo: | 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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