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Abstract：
Alzheimer\'s disease (AD) is the most common cause of dementia, characterized by progressive loss of cognitive function, with β-amyloid plaques and neurofibrillary tangles being its major pathological findings. Although the disease mainly affects the elderly, c. 5-10% of the cases are due to PSEN1, PSEN2, and APP mutations, principally associated with an early onset of the disease. The A413E (rs63750083) PSEN1 variant, identified in 2001, is associated with early-onset Alzheimer\'s disease (EOAD). Although there is scant knowledge about the disease\'s clinical manifestations and particular features, significant clinical heterogeneity was reported, with a high incidence of spastic paraparesis (SP), language impairments, and psychiatric and motor manifestations. This scoping review aims to synthesize findings related to the A431E variant of PSEN1. In the search, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the guidelines proposed by Arksey and O\'Malley. We searched and identified 247 studies including the A431E variant of PSEN1 from 2001 to 2021 in five databases and one search engine. After the removal of duplicates, and apply inclusion criteria, 42 studies were finally included. We considered a narrative synthesis with a qualitative approach for the analysis of the data. Given the study sample conformation, we divided the results into those carried out only with participants carrying A431E (seven studies), subjects with PSEN variants (11 studies), and variants associated with EOAD in PSEN1, PSEN2, and APP (24 studies). The resulting synthesis indicates most studies involve Mexican and Mexican-American participants in preclinical stages. The articles analyzed included carrier characteristics in categories such as genetics, clinical, imaging techniques, neuropsychology, neuropathology, and biomarkers. Some studies also considered family members\' beliefs and caregivers\' experiences. Heterogeneity in both the studies found and carrier samples of EOAD-related gene variants does not allow for the generalization of the findings. Future research should focus on reporting data on the progression of carrier characteristics through time and reporting results independently or comparing them across variants.
摘要：
阿尔茨海默病(AD)是痴呆的最常见原因,以认知功能逐渐丧失为特征，β-淀粉样斑块和神经原纤维缠结是其主要病理发现。虽然这种疾病主要影响老年人，c.5-10％的病例是由于PSEN1，PSEN2和APP突变，主要与疾病的早期发作有关。A413E(rs63750083)PSEN1变体,2001年发现，与早发性阿尔茨海默病(EOAD)有关。虽然对该疾病的临床表现和特定特征知之甚少，报告了显著的临床异质性，痉挛性轻瘫（SP）的发生率很高，语言障碍，以及精神病和运动表现。本范围审查旨在综合与PSEN1的A431E变体相关的发现。在搜索中,我们遵循了系统评价和荟萃分析的首选报告项目(PRISMA)声明和Arksey和O'Malley提出的指南。我们在五个数据库和一个搜索引擎中搜索并确定了247项研究，包括2001年至2021年PSEN1的A431E变体。删除副本后，并应用纳入标准，最终纳入42项研究。我们考虑了用定性方法分析数据的叙事综合。鉴于研究样本的构象，我们将结果分为仅对携带A431E的参与者进行的结果（七项研究），具有PSEN变异的受试者（11项研究），以及PSEN1、PSEN2和APP中与EOAD相关的变异(24项研究)。由此产生的综合表明，大多数研究涉及处于临床前阶段的墨西哥和墨西哥裔美国人参与者。分析的文章包括遗传学等类别的载体特征，临床,成像技术，神经心理学,神经病理学，和生物标志物。一些研究还考虑了家庭成员的“信念和照顾者”的经历。在EOAD相关基因变体的研究和携带者样本中的异质性不允许发现的推广。未来的研究应侧重于报告载体特征随时间进展的数据，并独立报告结果或在变体之间进行比较。
