The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Temporal lobe functional activity and connectivity in young adult APOE ɛ4 carriers
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., Mazoyer, B., & Joliot, M. (2002) · NeuroImage · doi:10.1006/nimg.2001.0978 · Cited by 16,319
Statistical Methods for Research Workers
Fisher, R. A. (1945) · American Journal of Clinical Pathology · doi:10.1093/ajcp/15.11.552b · Cited by 10,883
Voxel-Based Morphometry—The Methods
Ashburner, J., & Friston, K. J. (2000) · NeuroImage · doi:10.1006/nimg.2000.0582 · Cited by 8,676
Snodgrass, J. G., & Vanderwart, M. (1980) · Journal of Experimental Psychology Human Learning & Memory · doi:10.1037//0278-7393.6.2.174 · Cited by 5,604
A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains
Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N. A., Friston, K. J., & Frackowiak, R. S. J. (2001) · NeuroImage · doi:10.1006/nimg.2001.0786 · Cited by 4,561
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
Pleiotropy, natural selection, and the evolution of senescence.
Williams, G. C. (1957) · Evolution · doi:10.1111/j.1558-5646.1957.tb02911.x · Cited by 4,279
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786
Snodgrass, J. G., & Vanderwart, M. (1980) · Journal of Experimental Psychology Human Learning & Memory · doi:10.1037/0278-7393.6.2.174 · Cited by 3,635
Forman, S. D., Cohen, J. D., Fitzgerald, M., Eddy, W. F., Mintun, M. A., & Noll, D. C. (1995) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910330508 · Cited by 3,202
Distinct patterns of brain activity in young carriers of the APOE -ε4 allele
Filippini, N., MacIntosh, B. J., Hough, M. G., Goodwin, G. M., Frisoni, G. B., Smith, S. M., Matthews, P. M., Beckmann, C. F., & Mackay, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811879106 · Cited by 1,613
Patterns of Brain Activation in People at Risk for Alzheimer's Disease
Bookheimer, S. Y., Strojwas, M. H., Cohen, M. S., Saunders, A. M., Pericak-Vance, M. A., Mazziotta, J. C., & Small, G. W. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008173430701 · Cited by 1,328
Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease
Jack, C. R., Petersen, R. C., Xu, Y. C., Waring, S. C., O'Brien, P. C., Tangalos, E. G., Smith, G. E., Ivnik, R. J., & Kokmen, E. (1997) · Neurology · doi:10.1212/wnl.49.3.786 · Cited by 1,128
Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2635903100 · Cited by 977
Statistical Methods for Research Workers
Tukey, J. W., & Fisher, R. A. (1952) · Econometrica · doi:10.2307/1907425 · Cited by 950
Measuring functional connectivity during distinct stages of a cognitive task
Rissman, J., Gazzaley, A. H., & D’Esposito, M. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.06.035 · Cited by 917
Observing the transformation of experience into memory
Paller, K. A., & Wagner, A. D. (2002) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(00)01845-3 · Cited by 852
Staging of Alzheimer-Related Cortical Destruction
Braak, H., Braak, E., & Bohl, J. (2008) · European Neurology · doi:10.1159/000116984 · Cited by 836 · cited 1×
“Studies of functional, structural, and behavioral differences associated with variants of the APOE genotype have focused on the MTL, based on abundant evidence identifying the MTL as the earliest site of AD-associated pathology [22].”
BackgroundFunctional deactivations: Change with age and dementia of the Alzheimer type
Lustig, C., Snyder, A. Z., Bhakta, M., O'Brien, K. C., McAvoy, M., Raichle, M. E., Morris, J. C., & Buckner, R. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235925100 · Cited by 720
Evolution of the neuropathology of Alzheimer's disease
Braak, H., & Braak, E. (1996) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1996.tb05866.x · Cited by 710
Medial temporal lobe function and structure in mild cognitive impairment
Dickerson, B. C., Salat, D. H., Bates, J. F., Atiya, M., Killiany, R., Greve, D. N., Dale, A. M., Stern, C. E., Blacker, D., Albert, M., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20163 · Cited by 579
Handbook of Functional Neuroimaging of Cognition
Grady, C. L. (2006) · The MIT Press eBooks · doi:10.7551/mitpress/3420.001.0001 · Cited by 536
Reelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524
Statistical Methods for Research Workers
H., F. Z. (1932) · Agronomy Journal · doi:10.2134/agronj1932.00021962002400120011x · Cited by 515
Dickerson, B. C., Goncharova, I. I., Sullivan, M., Forchetti, C., Wilson, R. S., Bennett, D. A., Beckett, L. A., & deToledo‐Morrell, L. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00271-8 · Cited by 495
Evolution of neuronal changes in the course of Alzheimer’s disease
Braak, H., & Braak, E. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6467-9_11 · Cited by 493
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500579102 · Cited by 401
Effects of Healthy Aging on Hippocampal and Rhinal Memory Functions: An Event-Related fMRI Study
Daselaar, S. M., Fleck, M. S., Dobbins, I. G., Madden, D. J., & Cabeza, R. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhj112 · Cited by 392
Self-citationfMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease
Bondi, M. W., Houston, W. S., Eyler, L. T., & Brown, G. G. (2005) · Neurology · doi:10.1212/01.wnl.0000150885.00929.7e · Cited by 372
Sperling, R. A., Chua, E. F., Cocchiarella, A. J., Rand‐Giovannetti, E., Poldrack, R. A., Schacter, D. L., & Albert, M. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00391-4 · Cited by 370
Comparison of memory fMRI response among normal, MCI, and Alzheimer’s patients
Machulda, M. M., Ward, H. A., Borowski, B., Gunter, J. L., H., R., O’Brien, P. C., Petersen, R. C., Boeve, B. F., Knopman, D. S., Tang‐Wai, D. F., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000079052.01016.78 · Cited by 354
Effects of aging on the neural correlates of successful item and source memory encoding.
Dennis, N. A., Hayes, S. M., Prince, S. E., Madden, D. J., Huettel, S. A., & Cabeza, R. E. L. (2008) · Journal of Experimental Psychology Learning Memory and Cognition · doi:10.1037/0278-7393.34.4.791 · Cited by 314
Self-citationTervo, S., Kivipelto, M., Hänninen, T., Vanhanen, M., Hallikainen, M., Mannermaa, A., & Soininen, H. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000076356 · Cited by 298
Better Memory and Neural Efficiency in Young Apolipoprotein E 4 Carriers
Mondadori, C. R. A., de Quervain, D. J. ‐., Buchmann, A., Mustovic, H., Wollmer, M. A., Schmidt, C. F., Boesiger, P., Hock, C., Nitsch, R. M., Papassotiropoulos, A., et al. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhl103 · Cited by 277
Shaw, P., Lerch, J. P., Pruessner, J. C., Taylor, K. N., Rose, A. B., Greenstein, D., Clasen, L., Evans, A., Rapoport, J. L., & Giedd, J. N. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70106-0 · Cited by 257
Trivedi, M. A., Schmitz, T. W., Ries, M. L., Torgerson, B. M., Sager, M. A., Hermann, B. P., Asthana, S., & Johnson, S. C. (2006) · BMC Medicine · doi:10.1186/1741-7015-4-1 · Cited by 215
Combining Brains: A Survey of Methods for Statistical Pooling of Information
Lazar, N. A., Luna, B., Sweeney, J. A., & Eddy, W. F. (2002) · NeuroImage · doi:10.1006/nimg.2002.1107 · Cited by 208
Rémy, F., Mirrashed, F., Campbell, B. I., & Richter, W. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.10.045 · Cited by 200
Conversion to dementia from mild cognitive disorder
Tschanz, J. T., Welsh-Bohmer, K. A., Lyketsos, C. G., Corcoran, C. M., Green, R. C., Hayden, K. M., Norton, M. C., Zandi, P. P., Toone, L., West, N. A., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000224748.48011.84 · Cited by 181
Self-citationKircher, T. T. J., Weis, S., Freymann, K., Erb, M., Jessen, F., Grodd, W., Heun, R., & Leube, D. (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.104877 · Cited by 177
Koch, W., Ehrenhaft, A., Grießer, K., Pfeufer, A., Mueller, J. C., Schömig, A., & Kastrati, A. (2002) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2002.197 · Cited by 169
Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis
Han, S. D., & Bondi, M. W. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.02.006 · Cited by 158
Han, S. D., Houston, W. S., Jak, A. J., Eyler, L. T., Nagel, B. J., Fleisher, A., Brown, G. G., Corey‐Bloom, J., Salmon, D. P., Thal, L. J., et al. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.12.013 · Cited by 156
Wishart, H. A., Saykin, A. J., Rabin, L. A., Santulli, R. B., Flashman, L. A., Guerin, S. J., Mamourian, A. C., Belloni, D. R., Rhodes, C. H., & McAllister, T. W. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1603 · Cited by 151
Mori, E., Yoneda, Y., Yamashita, H., Hirono, N., Ikeda, M., & Yamadori, A. (1997) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.63.2.214 · Cited by 140
Correlations Between Apolipoprotein E ε4 Gene Dose and Whole Brain Atrophy Rates
Chen, K., Reiman, E. M., Alexander, G. E., Caselli, R. J., Gerkin, R. D., Bandy, D. J., Domb, A., Osborne, D., Fox, N. C., Crum, W. R., et al. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.916 · Cited by 121
Morishima-Kawashima, M., Oshima, N., Ogata, H., Yamaguchi, H., Yoshimura, M., Sugihara, S., & Ihara, Y. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64847-x · Cited by 119
APOE related alterations in cerebral activation even at college age
Scarmeas, N. (2005) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.053645 · Cited by 97
Han, S. D., Drake, A., Cessante, L. M., Jak, A. J., Houston, W. S., Delis, D. C., Filoteo, J. V., & Bondi, M. W. (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.108183 · Cited by 94
Prognostic Value of Posteromedial Cortex Deactivation in Mild Cognitive Impairment
Petrella, J. R., Prince, S. E., Wang, L., Hellegers, C., & Doraiswamy, P. M. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001104 · Cited by 87
Distinct patterns of brain activity in young carriers of the APOE e4 allele
Filippini, N., MacIntosh, B., Hough, M., Goodwin, G. M., Frisoni, G. B., Ebmeier, K. P., Smith, S. M., Matthews, P. M., Beckmann, C. F., & Mackay, C. (2009) · NeuroImage · doi:10.1016/s1053-8119(09)71381-3 · Cited by 81
Qiu, S., Korwek, K. M., & Weeber, E. J. (2005) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2005.08.009 · Cited by 63
Predictive Value of APOE Genotyping in Incipient Alzheimer's Diseasesa
Petersen, R. C., Waring, S. C., Smith, G. E., Tangalos, E. G., & Thibodeau, S. N. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb32599.x · Cited by 58
Filbey, F. M., Slack, K. J., Sunderland, T., & Cohen, R. M. (2006) · Neuroreport · doi:10.1097/01.wnr.0000234745.27571.d1 · Cited by 51
Stout, J. C., Bondi, M. W., Jernigan, T. L., Archibald, S. L., Delis, D. C., & Salmon, D. P. (1999) · Neuropsychology · doi:10.1037//0894-4105.13.2.188 · Cited by 48
Stout, J. C., Bondi, M. W., Jernigan, T. L., et al. (1999) · Neuropsychology · doi:10.1037/0894-4105.13.2.188 · Cited by 39
Functional Neuroimaging of Episodic Memory
Gabrieli, J. D. E. (2006) · The MIT Press eBooks · doi:10.7551/mitpress/3420.003.0011 · Cited by 26
Neural correlates of differential retrieval orientation: Sustained and item-related components
Woodruff, C. C., Uncapher, M. R., & Rugg, M. D. (2006) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2006.06.019 · Cited by 26
Functional MRI in the early diagnosis of Alzheimer’s disease: is it time to refocus?
Prince, S. E., Woo, S. L., Doraiswamy, P. M., & Petrella, J. R. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.2.169 · Cited by 14
Cited by
Sorted by citations
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758
The cognitive neuroscience of ageing
Grady, C. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3256 · Cited by 1,286
Reduction of Hippocampal Hyperactivity Improves Cognition in Amnestic Mild Cognitive Impairment
Bakker, A., Krauss, G. L., Albert, M., Speck, C. L., Jones, L. R., Stark, C. E. L., Yassa, M. A., Bassett, S. S., Shelton, A. L., & Gallagher, M. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.023 · Cited by 940
Apolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases
Huang, Y., & Mahley, R. W. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.025 · Cited by 829
Bateman, R. J., Aisen, P. S., De Strooper, B., Fox, N. C., Lemere, C. A., Ringman, J. M., Salloway, S., Sperling, R. A., Windisch, M., & Xiong, C. (2010) · Alzheimer's Research & Therapy · doi:10.1186/alzrt59 · Cited by 573
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
