Orozco-Barajas Maribel, Oropeza-Ruvalcaba Yulisa, Canales-Aguirre Alejandro A, Sánchez-González Victor J
Doctorado en Biociencias, Centro Universitario de los Altos, Universidad de Guadalajara, Guadalajara, Mexico.
Centro de Atención Psicológica, Tepatitlán de Morelos, Mexico.
Front Aging Neurosci. 2022 Jul 22;14:860529. doi: 10.3389/fnagi.2022.860529. eCollection 2022.
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 , , and mutations, principally associated with an early onset of the disease. The A413E (rs63750083) 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 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 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 variants (11 studies), and variants associated with EOAD in , , and (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.
阿尔茨海默病（AD）是痴呆最常见的病因，其特征为认知功能进行性丧失，β-淀粉样蛋白斑块和神经原纤维缠结是其主要病理表现。尽管该疾病主要影响老年人，但约5%-10%的病例归因于 、 和 基因突变，主要与疾病的早发相关。2001年鉴定出的A413E（rs63750083）变异与早发性阿尔茨海默病（EOAD）相关。尽管对该疾病的临床表现和特殊特征了解甚少，但据报道存在显著的临床异质性，痉挛性截瘫（SP）、语言障碍以及精神和运动表现的发生率较高。本综述旨在综合与 基因A431E变异相关的研究结果。在检索过程中我们遵循系统评价与Meta分析的首选报告项目（PRISMA）声明以及阿克西和奥马利提出的指南。我们在五个数据库和一个搜索引擎中检索并识别出2001年至2021年期间包含 基因A431E变异的247项研究。在去除重复项并应用纳入标准后，最终纳入42项研究。我们采用定性方法进行叙述性综合分析数据。鉴于研究样本构成，我们将结果分为仅针对携带A431E的参与者开展的研究（7项研究）、携带 基因变异的受试者（11项研究）以及与 、 和 基因中与EOAD相关的变异（24项研究）。综合结果表明，大多数研究涉及临床前阶段的墨西哥和墨西哥裔美国参与者。分析的文章包括遗传学、临床、成像技术、神经心理学、神经病理学和生物标志物等类别的携带者特征。一些研究还考虑了家庭成员的信念和护理人员的经历。所发现的研究以及EOAD相关基因变异携带者样本中的异质性使得研究结果无法一概而论。未来的研究应侧重于报告携带者特征随时间的进展数据，并独立报告结果或跨变异进行比较。
