Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease
Open accessAbstract
The ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of ε4 carriers ( n = 67) vs. noncarriers ( n = 24) with mild AD from the Alzheimer’s Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.
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The ApoE gene encodes a protein responsible for lipid transport.
“The ApoE gene encodes for a protein responsible for lipid transport; ε4 allele carriers have increased deposition of amyloid and also show adverse effects on memory and executive function [70].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [70]
ε4 allele carriers have increased deposition of amyloid and adverse effects on memory and executive function.
“The ApoE gene encodes for a protein responsible for lipid transport; ε4 allele carriers have increased deposition of amyloid and also show adverse effects on memory and executive function [70].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [70]
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- Authors
- Wolk, D. A., Dickerson, B. C., Initiative, T. A. D. N., Weiner, M., Aiello, M., Aisen, P., Albert, M. S., Alexander, G., Anderson, H. S., Anderson, K., Apostolova, L., Arnold, S., Ashford, W., Assaly, M., Asthana, S., Bandy, D., Bartha, R., Bates, V., Beckett, L., Bell, K. L., Benincasa, A. L., Bergman, H., Bernick, C., Bernstein, M., Black, S., Blank, K., Borrie, M., Brand, C., Brewer, J., Brown, A. D., Burns, J. M., Cairns, N. J., Caldwell, C., Capote, H., Carlsson, C. M., Carmichael, O., Cellar, J. S., Celmins, D., Chen, K., Chertkow, H., Chowdhury, M., Clark, D., Connor, D., Correia, S., Crawford, K., Dale, A., de Leon, M. J., De Santi, S. M., DeCarli, C., deToledo-Morrell, L., DeVous, M., Diaz-Arrastia, R., Dolen, S., Donohue, M., Doody, R. S., Doraiswamy, P. M., Duara, R., Englert, J., Farlow, M., Feldman, H., Felmlee, J., Fleisher, A., Fletcher, E., Foroud, T. M., Foster, N., Fox, N., Frank, R., Gamst, A., Given, C. A., Graff-Radford, N. R., Green, R. C., Griffith, R., Grossman, H., Hake, A. M., Hardy, P., Harvey, D., Heidebrink, J. L., Hendin, B. A., Herring, S., Honig, L. S., Hosein, C., Robin Hsiung, G.-Y., Hudson, L., Ismail, M. S., Jack, C. R., Jacobson, S., Jagust, W., Jayam-Trouth, A., Johnson, K., Johnson, H., Johnson, N., Johnson, K., Johnson, K. A., Johnson, S., Kachaturian, Z., Karlawish, J. H., Kataki, M., Kaye, J., Kertesz, A., Killiany, R., Kittur, S., Koeppe, R. A., Korecka, M., Kornak, J., Kozauer, N., Lah, J. J., Laubinger, M. M., Lee, V. M.-Y., Lee, T.-Y., Lerner, A., Levey, A. I., Longmire, C. F., Lopez, O. L., Lord, J. L., Lu, P. H., MacAvoy, M. G., Malloy, P., Marson, D., Martin-Cook, K., Martinez, W., Marzloff, G., Mathis, C., Mc-Adams-Ortiz, C., Mesulam, M., Miller, B. L., Mintun, M. A., Mintzer, J., Molchan, S., Montine, T., Morris, J., Mulnard, R. A., Munic, D., Nair, A., Neu, S., Nguyen, D., Norbash, A., Oakley, M., Obisesan, T. O., Ogrocki, P., Ott, B. R., Parfitt, F., Pawluczyk, S., Pearlson, G., Petersen, R., Petrella, J. R., Potkin, S., Potter, W. Z., Preda, A., Quinn, J., Rainka, M., Reeder, S., Reiman, E. M., Rentz, D. M., Reynolds, B., Richard, J., Roberts, P., Rogers, J., Rosen, A., Rosen, H. J., Rusinek, H., Sabbagh, M., Sadowsky, C., Salloway, S., Santulli, R. B., Saykin, A. J., Scharre, D. W., Schneider, L., Schneider, S., Schuff, N., Shah, R. C., Shaw, L., Shen, L., Silverman, D. H. S., Simpson, D. M., Sink, K. M., Smith, C. D., Snyder, P. J., Spann, B. M., Sperling, R. A., Spicer, K., Stefanovic, B., Stern, Y., Stopa, E., Tang, C., Tariot, P., Taylor-Reinwald, L., Thai, G., Thomas, R. G., Thompson, P., Tinklenberg, J., Toga, A. W., Tremont, G., Trojanowki, J. Q., Trost, D., Turner, R. S., van Dyck, C. H., Vanderswag, H., Varon, D., Villanueva-Meyer, J., Villena, T., Walter, S., Wang, P., Watkins, F., Weiner, M., Williamson, J. D., Wolk, D., Wu, C.-K., Zerrate, M., & Zimmerman., E. A.
- Affiliations
- Department of Neurology,
- Harvard University (US)
- University of Pennsylvania (US)
- ORCID
- Dickerson, Bradford C.
- Aisen, Paul
- Albert, Marilyn S.
- Alexander, Gene
- Apostolova, Liana
- Asthana, Sanjay
- Beckett, Laurel
- Bell, Karen L.
- Bergman, Howard
- Bernick, Charles
- Black, Sandra
- Burns, Jeffrey M.
- Cairns, Nigel J.
- Carlsson, Cynthia M.
- Carmichael, Owen
- Chen, Kewei
- Chertkow, Howard
- Clark, David
- Correia, Stephen
- Crawford, Karen
- Dale, Anders
- DeCarli, Charles
- DeVous, Michael
- Diaz-Arrastia, Ramon
- Donohue, Michael
- Doraiswamy, P. Murali
- Duara, Ranjan
- Farlow, Martin
- Feldman, Howard
- Felmlee, Joel
- Fleisher, Adam
- Foroud, Tatiana M.
- Fox, Nick
- Green, Robert C.
- Hake, Ann M.
- Hardy, Peter
- Harvey, Danielle
- Heidebrink, Judith L.
- Hendin, Barry A.
- Honig, Lawrence S.
- Ismail, M. Saleem
- Jack, Clifford R.
- Jacobson, Sandra
- Jagust, William
- Johnson, Kris
- Johnson, Heather
- Johnson, Nancy
- Johnson, Keith A.
- Johnson, Sterling
- Karlawish, Jason H.
- Kataki, Maria
- Kaye, Jeffrey
- Kertesz, Andrew
- Killiany, Ronald
- Koeppe, Robert A.
- Korecka, Magdalena
- Kornak, John
- Lah, James J.
- Lee, Virginia M.-Y.
- Lerner, Alan
- Levey, Allan I.
- Lord, Joanne L.
- Lu, Po H.
- Marson, Daniel
- Marzloff, George
- Mesulam, Marsel
- Miller, Bruce L.
- Mintzer, Jacobo
- Morris, John
- Nair, Anil
- Nguyen, Dana
- Norbash, Alexander
- Obisesan, Thomas O.
- Ott, Brian R.
- Pearlson, Godfrey
- Petersen, Ronald
- Petrella, Jeffrey R.
- Potkin, Steven
- Preda, Adrian
- Reiman, Eric M.
- Rentz, Dorene M.
- Rosen, Allyson
- Rosen, Howard J.
- Rusinek, Henry
- Sabbagh, Marwan
- Salloway, Stephen
- Santulli, Robert B.
- Saykin, Andrew J.
- Scharre, Douglas W.
- Schneider, Lon
- Shah, Raj C.
- Shen, Li
- Silverman, Daniel H.S.
- Sink, Kaycee M.
- Smith, Charles D.
- Snyder, Peter J.
- Sperling, Reisa A.
- Stefanovic, Bojana
- Stern, Yaakov
- Tang, Cheuk
- Tariot, Pierre
- Thai, Gaby
- Thomas, Ronald G.
- Thompson, Paul
- Toga, Arthur W.
- Tremont, Geoffrey
- Turner, Raymond Scott
- Walter, Sarah
- Williamson, Jeff D.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-05-17
- Volume
- 107
- Issue
- 22
- Pages
- 10256-10261
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2890481
- OpenAlex
- W2074109912
- Cited by
- 248
- References
- 63
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 9 · 2023: 15 · 2022: 11 · 2021: 23 · 2020: 17 · 2019: 15 · 2018: 17 · 2017: 11 · 2016: 16 · 2015: 16 · 2014: 14 · 2013: 23 · 2012: 14
- FWCI
- 14.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, R21-AG29840, R01AG027342, R01AG022374, P30AG010124, R21AG029840, R01AG012101, R01 AG29411, P30AG019610, K23AG028018, P50AG005134, R01AG029411, U19AG010483)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- apolipoprotein E, APOE ε4, Alzheimer's disease, genetic risk factors, memory impairment, executive function, working memory, lexical access, medial temporal lobe atrophy, cortical thickness, hippocampal volume, large-scale brain networks, clinical phenotype, cerebrospinal fluid biomarkers, mild cognitive impairment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Atrophy, Attention, Cerebral Cortex, Female, Genotype, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Memory, Memory Disorders, Nerve Net, Apolipoprotein E4, Executive Function, Genetic Association Studies
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