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

Author(s):Show less -

Axelrud, Luiza Kvitko ^{[1, 2]} ; Sato, Joao Ricardo ^{[3, 2]} ; Santoro, Marcos Leite ^{[4, 2]} ; Talarico, Fernanda ^{[4, 2]} ; Pine, Daniel Samuel ^[5] ; Rohde, Luis Augusto ^{[1, 2]} ; Zugman, Andre ^{[6, 2]} ; Amaro, Jr., Edson ^{[7, 8]} ; Bressan, Rodrigo Affonseca ^{[6, 2]} ; Grassi-Oliveira, Rodrigo ^[9] ; Pan, Pedro Mario ^{[6, 2]} ; Hoffmann, Mauricio Scopel ^{[1, 2]} ; Simioni, Andre Rafael ^{[1, 2]} ; Martin Guinjoan, Salvador ^[10] ; Hakonarson, Hakon ^[11] ; Brietzke, Elisa ^[6] ; Gadelha, Ary ^{[6, 2]} ; da Silva, Renata Pellegrino ^[11] ; Hoexter, Marcelo Queiroz ^[8] ; Miguel, Euripedes Constantino ^{[2, 12]} ; Belangero, Sintia Iole ^{[4, 2]} ; Salum, Giovanni Abrahao ^{[1, 2]}

Affiliation:Show less -

^[1] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dept Psiquiatria & Med Legal, Sect Negat Affect & Social Proc, Porto Alegre, RS - Brazil

^[2] Natl Inst Dev Psychiat INPD, CNPq, Sao Paulo - Brazil

^[3] Univ Fed ABC, Ctr Matemat Comp & Cognicao, Santo Andre - Brazil

^[4] Univ Fed Sao Paulo UNIFESP, Dept Morfol & Genet, Sao Paulo - Brazil

^[5] NIMH, Intramural Res Program, Emot & Dev Branch, Bethesda, MD 20892 - USA

^[6] Univ Fed Sao Paulo, Dept Psiquiatria, Sao Paulo - Brazil

^[7] Hosp Israelita Albert Einstein, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Dept Radiol, Sao Paulo - Brazil

^[9] Pontifical Catholic Univ Rio Grande Sul PUCRS, Dev Cognit Neurosci Res Grp GNCD, Porto Alegre, RS - Brazil

^[10] Univ Buenos Aires, Sch Med & Psychol, Buenos Aires, DF - Argentina

^[11] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 - USA

^[12] Univ Sao Paulo, Dept Psiquiatria, Sao Paulo - Brazil

• Document type: Journal article
• Source: NEUROBIOLOGY OF AGING; v. 82, p. 10-17, OCT 2019.
• Web of Science Citations: 1

Abstract

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 Sao 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: beta = 0.180, p(adjusted) = 0.036; replication sample: beta = 0.202, p = 0.031). This connectivity was also associated with inhibitory control (beta = 0.157, p(adjusted) = 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. (C) 2019 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 08/57896-8 - National Institute for Developmental Psychiatry
• Grantee: Eurípedes Constantino Miguel Filho
• Support Opportunities: Research Projects - Thematic Grants