TY - JOUR
T1 - Interactive effects of the APOE and BDNF polymorphisms on functional brain connectivity
T2 - the Tasmanian Healthy Brain Project
AU - Pietzuch, Manuela
AU - Bindoff, Aidan
AU - Jamadar, Sharna
AU - Vickers, James C.
N1 - Funding Information:
Funding for the Wicking Centre is provided by the J.O. and J.R. Wicking Trust (Equity Trustees). Sharna Jamadar is supported by an Australian National Health and Medical Research Council Fellowship APP1174164
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Resting-state functional magnetic resonance imaging measures pathological alterations in neurodegenerative diseases, including Alzheimer’s disease. Disruption in functional connectivity may be a potential biomarker of ageing and early brain changes associated with AD-related genes, such as APOE and BDNF. The objective of this study was to identify group differences in resting-state networks between individuals with BDNF Val66Met and APOE polymorphisms in cognitively healthy older persons. Dual regression following Independent Components Analysis were performed to examine differences associated with these polymorphisms. APOE ε3 homozygotes showed stronger functional connectivity than APOE ε4 carriers. Males showed stronger functional connectivity between the Default Mode Network (DMN) and grey matter premotor cortex, while females showed stronger functional connectivity between the executive network and lateral occipital cortex and parahippocampal gyrus. Additionally, we found that with increasing cognitive reserve, functional connectivity increased within the Dorsal Attention Network (DAN), but decreased within the DMN. Interaction effects indicated stronger functional connectivity in Met/ε3 carriers than in Met/ε4 and Val/ε4 within both the DMN and DAN. APOE/BDNF interactions may therefore influence the integrity of functional brain connections in older adults, and may underlie a vulnerable phenotype for subsequent Alzheimer’s-type dementia.
AB - Resting-state functional magnetic resonance imaging measures pathological alterations in neurodegenerative diseases, including Alzheimer’s disease. Disruption in functional connectivity may be a potential biomarker of ageing and early brain changes associated with AD-related genes, such as APOE and BDNF. The objective of this study was to identify group differences in resting-state networks between individuals with BDNF Val66Met and APOE polymorphisms in cognitively healthy older persons. Dual regression following Independent Components Analysis were performed to examine differences associated with these polymorphisms. APOE ε3 homozygotes showed stronger functional connectivity than APOE ε4 carriers. Males showed stronger functional connectivity between the Default Mode Network (DMN) and grey matter premotor cortex, while females showed stronger functional connectivity between the executive network and lateral occipital cortex and parahippocampal gyrus. Additionally, we found that with increasing cognitive reserve, functional connectivity increased within the Dorsal Attention Network (DAN), but decreased within the DMN. Interaction effects indicated stronger functional connectivity in Met/ε3 carriers than in Met/ε4 and Val/ε4 within both the DMN and DAN. APOE/BDNF interactions may therefore influence the integrity of functional brain connections in older adults, and may underlie a vulnerable phenotype for subsequent Alzheimer’s-type dementia.
UR - http://www.scopus.com/inward/record.url?scp=85110585732&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-93610-0
DO - 10.1038/s41598-021-93610-0
M3 - Article
C2 - 34267235
AN - SCOPUS:85110585732
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 14514
ER -