ArticleCerebral cortex (New York, N.Y. : 1991)2023
Genotypic effects of APOE-ε4 on resting-state connectivity in cognitively intact individuals support functional brain compensation.
Article in Cerebral cortex (New York, N.Y. : 1991), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Genetic risk of Alzheimer's disease is associated with loss of brain network segregation in midlife.Communications biology · 2026Article
- Ventral hippocampal-postcentral gyrus functional connectivity mediates the association of APOE ε4 gene dose, depressive symptoms, and cognitive function in mild cognitive impairment with subsyndromal depression.Frontiers in aging neuroscience · 2026Article
- Longitudinal functional connectivity during rest and task is differentially related to Alzheimer's pathology and episodic memory in older adults.Scientific reports · 2025Article
- Glucose metabolism in hyper-connected regions predicts neurodegeneration and speed of conversion in Alzheimer's disease.European journal of nuclear medicine and molecular imaging · 2025Article
- Differential effects of aging, Alzheimer's pathology, and APOE4 on longitudinal functional connectivity and episodic memory in older adults.Alzheimer's research & therapy · 2025Article
- Connectivity, Pathology, and ApoE4 Interactions Predict Longitudinal Tau Spatial Progression and Memory.Human brain mapping · 2024Article
- Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Interactions between physical exercise, associative memory, and genetic risk for Alzheimer's disease.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Associations between Education Years and Resting-state Functional Connectivity Modulated byClinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Article
- Article
- Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.Alzheimer's research & therapy · 2023Article
- Altered nucleus accumbens functional connectivity precedes apathy in Parkinson's disease.Brain : a journal of neurology · 2023Article
- The relative contribution of modifiable and non-modifiable factors for determining cognition in mid-life individuals at risk for late-life Alzheimer's disease.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Abstract
The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer's disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the ε4 allele. Yet, no study has assessed APOE-ε4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-ε4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of ε4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found a reduced rsFC as a function of the APOE-ε4 allelic load in the temporal default-mode and the medial temporal networks, while recessive effects were found in the extrastriate and limbic networks. Some of these results were replicated in a subsample with negative amyloid markers. Interaction with cognitive data suggests that such a network reorganization may support cognitive performance in the ε4-homozygotes. Our data indicate that APOE-ε4 shapes the functional architecture of the resting brain and favor the idea of a network-based functional compensation.
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