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

• Published in: Neurobiology of aging Vol. 82; pp. 10 - 17
• Main Authors: Axelrud, Luiza Kvitko, Sato, João Ricardo, Santoro, Marcos Leite, Talarico, Fernanda, Pine, Daniel Samuel, Rohde, Luis Augusto, Zugman, Andre, Junior, Edson Amaro, Bressan, Rodrigo Affonseca, Grassi-Oliveira, Rodrigo, Pan, Pedro Mario, Hoffmann, Maurício Scopel, Simioni, Andre Rafael, Guinjoan, Salvador Martin, Hakonarson, Hakon, Brietzke, Elisa, Gadelha, Ary, Pellegrino da Silva, Renata, Hoexter, Marcelo Queiroz, Miguel, Euripedes Constantino, Belangero, Sintia Iole, Salum, Giovanni Abrahão
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2019
• Subjects: Adolescent; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Brain - diagnostic imaging; Brazil - epidemiology; Child; Cross-Sectional Studies; Female; Functional connectivity; Functional Neuroimaging - methods; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Humans; Male; Nerve Net - diagnostic imaging; Polygenic risk score; Polymorphism, Single Nucleotide - genetics; Tau protein; Brazil; Polygenic risk score; Functional connectivity; Tau protein; Alzheimer's disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.06.011

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.
•AD-PRS was associated with right precuneus and right superior temporal gyrus connectivity in youth.•This connectivity was associated with inhibitory control.•This connectivity also moderated the association between AD-PRS and memory.