Departamento de Psiquiatria e Medicina Legal, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Section on Negative Affect and Social Processes, Porto Alegre, Brazil; National Institute of Developmental Psychiatry (INPD, CNPq), São Paulo, Brazil.
National Institute of Developmental Psychiatry (INPD, CNPq), São Paulo, Brazil; Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, Santo André, Brazil.
Neurobiol Aging. 2019 Oct;82:10-17. doi: 10.1016/j.neurobiolaging.2019.06.011. Epub 2019 Jul 6.
Research suggested accumulation of tau proteins might lead to the degeneration of functional networks. Studies investigating the impact of genetic risk for Alzheimer's disease (AD) on early brain connections might shed light on mechanisms leading to AD development later in life. Here, we aim to investigate whether the polygenic risk score for Alzheimer's disease (AD-PRS) influences the connectivity among regions susceptible to tau pathology during childhood and adolescence. Participants were youth, aged 6-14 years, and recruited in Porto Alegre (discovery sample, n = 332) and São Paulo (replication sample, n = 304), Brazil. Subjects underwent genotyping and 6-min resting state funcional magnetic resonance imaging. Connections between the local maxima of tau pathology networks were used as dependent variables. The AD-PRS was associated with the connectivity between the right precuneus and the right superior temporal gyrus (discovery sample: β = 0.180, p = 0.036; replication sample: β = 0.202, p = 0.031). This connectivity was also associated with inhibitory control (β = 0.157, p = 0.035) and moderated the association between the AD-PRS and both immediate and delayed recall. These findings suggest the AD-PRS may affect brain connectivity in youth, which might impact memory performance and inhibitory control in early life.
研究表明，tau 蛋白的积累可能导致功能网络的退化。研究遗传因素对阿尔茨海默病（AD）的影响，可能有助于揭示导致 AD 发病的机制。本研究旨在探讨阿尔茨海默病的多基因风险评分（AD-PRS）是否会影响儿童和青少年时期易受 tau 病理学影响的区域之间的连接。参与者为来自巴西阿雷格里港（发现样本，n=332）和圣保罗（复制样本，n=304）的 6-14 岁的青少年。对受试者进行基因分型和 6 分钟静息状态功能磁共振成像。tau 病理学网络的局部最大值之间的连接被用作因变量。AD-PRS 与右侧顶下小叶和右侧颞上回之间的连接相关（发现样本：β=0.180，p=0.036；复制样本：β=0.202，p=0.031）。这种连接还与抑制控制相关（β=0.157，p=0.035），并调节了 AD-PRS 与即时和延迟回忆之间的关联。这些发现表明，AD-PRS 可能会影响年轻人的大脑连接，从而影响生命早期的记忆表现和抑制控制。
