Temporal lobe functional activity and connectivity in young adult APOE ɛ4 carriers
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Background: We sought to determine if the APOE ε4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTLs) during successful memory encoding in young adults. Methods: Twenty‐four healthy young adults, i.e., 12 carriers and 12 noncarriers of the APOE ε4 allele, were scanned in a subsequent‐memory paradigm, using event‐related functional magnetic resonance imaging. The neuroanatomic correlates of successful encoding were measured as greater neural activity for subsequently remembered versus forgotten task items, or in short, encoding success activity (ESA). Group differences in ESA within the MTLs, as well as whole‐brain functional connectivity with the MTLs, were assessed. Results: In the absence of demographic or performance differences, APOE ε4 allele carriers exhibited greater bilateral MTL activity relative to noncarriers while accomplishing the same encoding task. Moreover, whereas ε4 carriers demonstrated a greater functional connectivity of ESA‐related MTL activity with the posterior cingulate and other peri‐limbic regions, reductions in overall connectivity were found across the anterior and posterior cortices. Conclusions: These results suggest that the APOE ɛ4 allele may influence not only functional activations within the MTL, but functional connectivity of the MTLs to other regions implicated in memory encoding. Enhanced functional connectivity of the MTLs with the posterior cingulate in young adult ε4 carriers suggests that APOE may be expressed early in brain regions known to be involved in Alzheimer's disease, long before late‐onset dementia is a practical risk or consideration. These functional connectivity differences may also reflect pleiotropic effects of APOE during early development.
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Previous studies have already linked APOE4 to increased (hyper-)metabolism in young individuals.
“However, previous studies have already linked APOE4 to increased (hyper-)metabolism in young individuals.”
From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [44]
The Discussion reports greater memory-encoding-related hippocampal activity in young adult APOE ε4 carriers than in non-carriers and cites a similar finding in another young-adult study. The paper measures fMRI activity, however, not metabolism; its findings do not establish hypermetabolism. (LLM, conf=0.84)
Experimental — accuracy not yet measuredStudies in young adults, before the onset of a pathology, showed that APOE4 carriers display hypermetabolism and hyperactivity in distinct brain regions, such as the hippocampus, entorhinal cortex, and cortical regions.
“Studies in young adults, before the onset of a pathology, showed that APOE4 carriers display hypermetabolism and hyperactivity in distinct brain regions, such as the hippocampus, entorhinal cortex, and cortical regions [44,45,46].”
From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [44]
The Discussion (page not provided) reports greater memory-encoding activity in the hippocampus and parahippocampal gyrus of healthy young adult APOE ε4 carriers. It does not establish hypermetabolism or greater activity in the entorhinal cortex or other cortical regions; it instead reports reduced connectivity with other task-associated cortical regions. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHealthy young and middle-aged adult apoE4 carriers show increased hippocampal activation during encoding task performance.
“and increased hippocampal activation during encoding task performance [179–181]”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [181]
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- Authors
- Dennis, N. A., Browndyke, J. N., Stokes, J., Need, A., Burke, J. R., Welsh‐Bohmer, K. A., & Cabeza, R.
- Affiliations
- Pennsylvania State University (US)
- Duke University (US)
- Joseph and Kathleen Bryan Alzheimer's Disease Research Center Duke University Durham NC USA
- Corresponding author
- Browndyke, Jeffrey N.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2009-09-10
- Volume
- 6
- Issue
- 4
- Pages
- 303-311
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC2891943
- OpenAlex
- W2132091452
- Cited by
- 201
- References
- 57
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 11 · 2019: 12 · 2018: 8 · 2017: 13 · 2016: 12 · 2015: 11 · 2014: 27 · 2013: 14 · 2012: 17
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P30‐AG028377, R01‐AG23770, L30‐AG029001)
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- APOE ε4, medial temporal lobe
- MeSH terms
- Female, Genotype, Heterozygote, Hippocampus, Humans, Image Processing, Computer-Assisted, Functional Laterality, Magnetic Resonance Imaging, Male, Memory, Neural Pathways, Neuropsychological Tests, Photic Stimulation, Psychomotor Performance, Temporal Lobe, Reverse Transcriptase Polymerase Chain Reaction, Apolipoprotein E4, Young Adult
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