在一个老年社区样本中，皮质FADD蛋白减少与临床痴呆和认知衰退相关。

Decreased cortical FADD protein is associated with clinical dementia and cognitive decline in an elderly community sample.

作者信息

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, García-Fuster M Julia

机构信息

BC Mental Health and Addictions Research Institute, Vancouver, Canada.

Department of Psychiatry, University of British Columbia, Vancouver, Canada.

出版信息

Mol Neurodegener. 2017 Mar 20;12(1):26. doi: 10.1186/s13024-017-0168-x.

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.

背景

FADD（Fas相关死亡结构域）衔接蛋白是一种关键蛋白，参与细胞死亡的诱导，但也通过磷酸化形式（p-Ser194-FADD）介导非凋亡作用。本研究在一个老年社区样本中调查了FADD形式与年龄相关神经病理学、认知功能及痴呆几率之间的可能关联。

方法

在一项基于社区的衰老研究（记忆与衰老项目，MAP）的大量参与者队列的背外侧前额叶皮质（DLPFC）样本中，通过蛋白质免疫印迹分析对FADD形式进行定量，这些参与者未经历认知障碍（NCI，n = 51）、轻度认知障碍（MCI，n = 42）或痴呆（n = 57）。

结果

痴呆患者的皮质FADD水平较低，较低的FADD与更高的淀粉样β病理负荷、更少的突触前终末标志物、更差的认知功能以及更高的痴呆几率相关。结合在阿尔茨海默病大脑中观察到的FADD重新分布到斑块内的缠结和营养不良性神经突中，以及其在APP23小鼠皮质中的减少，结果表明这种多功能蛋白可能在疾病过程中参与连接淀粉样蛋白和tau病理的机制。