We have located links that may give you full text access.
Functional co-activation of the default mode network in APOE ε4-carriers: A replication study.
NeuroImage 2021 June 28
Structural and functional alterations of the brain in persons genetically at-risk for Alzheimer's disease (AD) are crucial in unravelling AD development. Filippini et al. found that the default mode network (DMN) is already affected in young APOE ε4-carriers, with increased co-activation of the DMN during rest and increased hippocampal task activation. We aimed to replicate the early findings of Filippini et al, using the APOE gene, still the principal AD risk gene, and extended this with a polygenic risk score (PRS) analysis for AD, using the Human Connectome Project dataset (HCP). We included participants from the HCP S1200 dataset (age range: 22-36 years). We studied morphometric features, functional DMN co-activation and functional task activation of recollection performance. Permutation Analysis of Linear Models (PALM) was used to test for group differences between APOE ε4-carriers and non-carriers, and to test the association with PRS. PALM controls for biases induced by the family structure of the HCP sample. Results were family-wise error rate corrected at p < 0.05. Our primary analysis did not replicate the early findings of Filippini et al. (2009). However, compared with non-carriers, APOE ε4-carriers showed increased functional activation during the encoding of subsequently recollected items in areas related to facial recognition (p<0.05, t>756.11). This increased functional activation was also positively associated with PRS (APOE variants included) (p<0.05, t>647.55). Our results are supportive for none to limited genetic effects on brain structure and function in young adults. Taking the methodological considerations of replication studies into account, the true effect of APOE ε4-carriership is likely smaller than indicated in the Filippini paper. However, it still holds that we may not yet be able to detect already present measurable effects decades before a clinical expression of AD. Since the mechanistic pathway of AD is likely to encompass many different factors, further research should be focused on the interactions of genetic risk, biomarkers, aging and lifestyle factors over the life course. Sensitive functional neuroimaging as used here may help disentangling these complex interactions.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app