载脂蛋白 E 基因 PSEN1 E280A 阿尔茨海默病认知衰退的遗传修饰剂。
Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease.
机构信息
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia.
出版信息
Alzheimers Dement. 2024 Apr;20(4):2873-2885. doi: 10.1002/alz.13754. Epub 2024 Mar 7.
INTRODUCTION
Rate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD.
METHODS
RCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole-exome sequencing for association with common exonic functional variants. Findings were validated in post mortem brain tissue.
RESULTS
One hundred seventy-two gene variants in FAD, and 227 gene variants in SAD associated with RCD. In FAD, performance decline of the immediate recall of the Rey-Osterrieth figure test associated with 122 genetic variants. Olfactory receptor OR51B6 showed the highest number of associated variants. Its expression was detected in temporal cortex neurons.
DISCUSSION
Impaired olfactory function has been associated with cognitive impairment in AD. Genetic variants in these or other genes could help to identify risk of faster memory decline in FAD and SAD patients.
简介
阿尔茨海默病（AD）的认知衰退率（RCD）决定了患者的受损程度和照顾者的负担程度。我们研究了 RCD 与 AD 中的遗传变异的关系。
方法
对 62 例家族性 AD（FAD）和 53 例散发性 AD（SAD）患者进行 RCD 评估，并通过全外显子组测序分析与常见外显子功能变异的关联。在死后脑组织中验证了研究结果。
结果
在 FAD 中，有 172 个基因变异与 RCD 相关，在 SAD 中，有 227 个基因变异与 RCD 相关。在 FAD 中，Rey-Osterrieth 图形测试的即时回忆表现与 122 个遗传变异相关。嗅觉受体 OR51B6 显示出最多数量的相关变异。其表达在颞叶皮层神经元中被检测到。
讨论
嗅觉功能受损与 AD 中的认知障碍有关。这些或其他基因中的遗传变异可能有助于识别 FAD 和 SAD 患者更快的记忆衰退风险。
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