背景：阿尔茨海默病（AD）是一种使人衰弱且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。虽然它有很高的遗传风险，由于PSEN2变化的EOAD是非常罕见的。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基因或风险基因的变异。方法和结果：在这项研究中，我们报道了一个35岁的女性携带PSEN2基因（c.640G>Tp.V214L）和ABCA7基因（c.2848G>Ap.V950M）的变异。先前报告的四例病例携带PSEN2V214L，无报告病例携带ABCA7V950M。她有偏头痛病史,卵圆孔未闭,无动脉瘤的自发性蛛网膜下腔出血,和多发性脑微出血。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变体进行了综述，并对患者特征进行总结和比较，为AD的临床诊断提供信息。
结论：对于不典型表现的病例，有必要进行基因筛查。
BACKGROUND: 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.
CONCLUSIONS: It is necessary to conduct genetic screening in cases with atypical manifestations.
