Genetic risk for Alzheimer's disease and functional brain connectivity in children and adolescents.

Genetic risk for Alzheimer's disease and functional brain connectivity in children and adolescents.
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DOI:
10.1016/j.neurobiolaging.2019.06.011
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发表时间:
2019-10
影响因子:
4.2
通讯作者:
Salum GA
Salum GA
中科院分区:
医学2区
文献类型:
--
作者:
Axelrud LK;Sato JR;Santoro ML;Talarico F;Pine DS;Rohde LA;Zugman A;Junior EA;Bressan RA;Grassi-Oliveira R;Pan PM;Hoffmann MS;Simioni AR;Guinjoan SM;Hakonarson H;Brietzke E;Gadelha A;Pellegrino da Silva R;Hoexter MQ;Miguel EC;Belangero SI;Salum GA

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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, padjusted = 0.036; replication sample: β = 0.202, p = 0.031). This connectivity was also associated with inhibitory control (β = 0.157, padjusted = 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.
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