Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, China.
Ningxia Hospital of Traditional Chinese Medicine, Ningxia, China.
Neurol Sci. 2023 Jun;44(6):1987-2001. doi: 10.1007/s10072-023-06602-5. Epub 2023 Jan 26.
Alzheimer's disease (AD) is a debilitating and highly heritable neurodegenerative disease. Early-onset AD (EOAD) was defined as AD occurring before age 65. Although it has a high genetic risk, EOAD due to PSEN2 variation is very rare. ABCA7 is an important risk gene for AD. Previously reported cases mainly carried variations in a single pathogenic or risk gene. METHODS AND RESULTS: In this study, we report a 35-year-old female carrying variants in both the PSEN2 gene (c.640G > T p.V214L) and ABCA7 gene (c.2848G > A p.V950M). Four previously reported cases carried PSEN2 V214L, and no reported cases carried ABCA7 V950M. She had a history of migraine, patent foramen ovale, spontaneous subarachnoid hemorrhage without aneurysm, and multiple cerebral microhemorrhages. Her MMSE score was 24/30, and her MoCA score was 22/30. The concentration of Aβ42 and the ratio of Aβ42 to Aβ40 in cerebral spinal fluid were obviously decreased. Published variants of PSEN2 and ABCA7 in PubMed were reviewed, and the patients' characteristics were summarized and compared to provide information for the clinical diagnosis of AD.
It is necessary to conduct genetic screening in cases with atypical manifestations.
阿尔茨海默病（AD）是一种使人衰弱且具有高度遗传性的神经退行性疾病。早发性 AD（EOAD）定义为 65 岁之前发生的 AD。尽管它具有很高的遗传风险，但 PSEN2 变异引起的 EOAD 非常罕见。ABCA7 是 AD 的重要风险基因。以前报道的病例主要携带单个致病性或风险基因的变异。方法和结果：在本研究中，我们报告了一名 35 岁女性，携带 PSEN2 基因（c.640G>T p.V214L）和 ABCA7 基因（c.2848G>A p.V950M）的变异。以前报道的 4 例病例携带 PSEN2 V214L，没有报道的病例携带 ABCA7 V950M。她有偏头痛、卵圆孔未闭、自发性蛛网膜下腔出血无动脉瘤和多发脑微出血的病史。她的 MMSE 评分为 24/30，MoCA 评分为 22/30。脑脊液中 Aβ42 的浓度和 Aβ42 与 Aβ40 的比值明显降低。对 PubMed 中已发表的 PSEN2 和 ABCA7 变异进行了审查，并对患者的特征进行了总结和比较，为 AD 的临床诊断提供信息。结论：对于表现不典型的病例，有必要进行遗传筛查。
