Department of Legal Medicine, Faculty of Medicine, University of Toyama, Toyama, Toyama, Japan.
Faculty of Medicine, University of Toyama, Toyama, Toyama, Japan.
Alzheimers Dement. 2024 Mar;20(3):2291-2296. doi: 10.1002/alz.13675. Epub 2024 Jan 12.
Neuropathological investigation of presymptomatic or early symptomatic presenilin-1 (PSEN1) mutation carriers in familial Alzheimer's disease (AD) is extremely scarce.
We report the autopsy findings of brothers with familial AD. Case 1 is a 45-year-old man without obvious cognitive impairment, who committed suicide. Case 2 is a 57-year-old older brother of Case 1 with advanced AD symptoms, who died of hypothermia during wondering.
In both cases, abundant amyloid plaques positive for amyloid β (Aβ) were found throughout the brain. Progression of neuronal loss and increasing amount and extension of neurofibrillary tangle pathology were evident in Case 2. Genetic investigation revealed a PSEN1_p. L392V mutation in both cases.
The present study shows a possible neuropathological boundary between symptomatic and preclinical AD with pathogenic PSEN1 mutation. Additional clinicopathological investigation for familial AD-related mutation carriers may be significant to explore the association between familial AD and suicide.
对家族性阿尔茨海默病（AD）中出现症状前或早期症状的早老素-1（PSEN1）突变携带者进行神经病理学研究极为罕见。
我们报告了两例家族性 AD 兄弟的尸检结果。病例 1 是一名 45 岁的男子，没有明显的认知障碍，自杀身亡。病例 2 是病例 1 的 57 岁的哥哥，有严重的 AD 症状，在徘徊时死于体温过低。
在这两例中，大脑中都发现了大量的淀粉样斑块，对淀粉样 β（Aβ）呈阳性。在病例 2 中，神经元丢失的进展和神经纤维缠结病理的数量和扩展明显增加。基因调查显示这两例均存在 PSEN1_p.L392V 突变。
本研究显示了具有致病性 PSEN1 突变的症状前和临床前 AD 之间可能存在神经病理学界限。对家族性 AD 相关突变携带者进行额外的临床病理研究，可能有助于探索家族性 AD 与自杀之间的关系。
