Hippocampal atrophy rates and CSF biomarkers in elderly APOE 2 normal subjects
Open accessAbstract
OBJECTIVE: To determine whether elderly normal APOE E2 (APOE2) carriers exhibit slower rates of hippocampal atrophy and memory decline compared to APOE3/3 carriers. We also determined whether APOE2 carriers have less Alzheimer pathology as reflected by CSF biomarkers. METHODS: We included longitudinal data from 134 cognitively normal individuals (27 APOE2/2 or E2/3, 107 APOE3/3) from the Alzheimer's Disease Neuroimaging Initiative, a prospective cohort study. A linear mixed-effects model was used to determine how APOE2 affected rates of hippocampal atrophy and cognitive change over time. In a subsample of 72 individuals who also underwent CSF analysis, an ordinary least-squares regression was used to determine whether CSF β-amyloid (Aβ), total tau, and phosphorylated tau-181 (p-tau) differed by APOE2 status. RESULTS: APOE2 carriers demonstrated slower rates of hippocampal atrophy (p = 0.004). The mean rate of hippocampal atrophy among APOE2 carriers was -33 mm(3)/year (95% confidence interval -65 to +0.4), or -0.5%/year, compared to -86 mm(3)/year (95% confidence interval -102 to -71), or -1.3%/year, in the APOE3/3 group. No differences in the rates of episodic memory (p = 0.23) or overall cognitive change (p = 0.90) were detected. In the CSF subsample, APOE2 carriers had higher levels of CSF Aβ (p = 0.01), lower p-tau (p = 0.02), and marginally lower tau (p = 0.12). CONCLUSION: A slower rate of hippocampal atrophy in normal APOE2 carriers is consistent with the lower risk of Alzheimer disease in these individuals. We hypothesize that the slower atrophy rate is related to decreased preclinical Alzheimer pathology.
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
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?
Some reports indicate slower hippocampal atrophy among APOE2 carriers.
“with some reports of slower hippocampal atrophy among APOE2 carriers [13].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882 · see citing works
Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., van der Kouwe, A., Killiany, R., Kennedy, D., Klaveness, S., et al. (2002) · Neuron · doi:10.1016/s0896-6273(02)00569-x · Cited by 8,610 · see citing works
The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods
Jack, C. R., Bernstein, M. A., Fox, N. C., Thompson, P., Alexander, G., Harvey, D., Borowski, B., Britson, P. J., L. Whitwell, J., Ward, C., et al. (2008) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21049 · Cited by 4,347 · see citing works
Self-citationAlzheimer's Disease Neuroimaging Initiative (ADNI)
Petersen, R. C., Aisen, P. S., Beckett, L. A., Donohue, M. C., Gamst, A. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Shaw, L. M., Toga, A. W., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181cb3e25 · Cited by 2,572 · see citing works
Self-citationProtective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Hansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., & Minthon, L. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70355-6 · Cited by 1,700 · see citing works
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment
Jack, C. R., Petersen, R. C., Xu, Y. C., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Waring, S. C., Tangalos, E. G., & Kokmen, E. (1999) · Neurology · doi:10.1212/wnl.52.7.1397 · Cited by 1,404 · see citing works
Self-citation<i>APOE</i> predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., & Mintun, M. A. (2010) · Annals of Neurology · doi:10.1002/ana.21843 · Cited by 830 · see citing works
Development of Cognitive Instruments for Use in Clinical Trials of Antidementia Drugs
Mohs, R. C., Knopman, D. S., Petersen, R. C., Ferris, S. H., Ernesto, C., Grundman, M., Sano, M., Bieliauskas, L. A., Geldmacher, D., Clark, C. M., et al. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199700112-00003 · Cited by 693 · see citing works
Self-citationMohs, R. C., Knopman, D. S., Petersen, R. C., Ferris, S. H., Ernesto, C., Grundman, M., Sano, M., Bieliauskas, L. A., Geldmacher, D., Clark, C., et al. (1997) · PubMed · Cited by 487 · see citing works
Self-citationA meta-analysis of hippocampal atrophy rates in Alzheimer's disease
Barnes, J., Bartlett, J. W., van de Pol, L. A., Loy, C. T., Scahill, R. I., Frost, C. D., Thompson, P. M., & Fox, N. C. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.01.010 · Cited by 396 · see citing works
Hippocampal volume as an index of Alzheimer neuropathology
Gosche, K. M., Mortimer, J. A., Smith, C. D., Markesbery, W. R., & Snowdon, D. A. (2002) · Neurology · doi:10.1212/wnl.58.10.1476 · Cited by 359 · see citing works
Shaw, P., Lerch, J. P., Pruessner, J. C., Taylor, K. N., Rose, A. B., GREENSTEIN, D. K., CLASEN, L. S., Evans, A. C., Rapoport, J. L., & Giedd, J. N. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70106-0 · Cited by 287 · see citing works
High frequency of apolipoprotein E ϵ2 Allele in hemorrhage due to cerebral amyloid angiopathy
Nicoll, J. A. R., Burnett, C., Love, S., Graham, D. I., Dewar, D., Ironside, J. W., Stewart, J., & Vinters, H. V. (1997) · Annals of Neurology · doi:10.1002/ana.410410607 · Cited by 284 · see citing works
The role of APOE -ε4 in longitudinal cognitive decline
Bretsky, P., Guralnik, J. M., Launer, L. J., Albert, M., & Seeman, T. E. (2003) · Neurology · doi:10.1212/01.wnl.0000055875.26908.24 · Cited by 257 · see citing works
Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele
Caselli, R. J., Reiman, E. M., Osborne, D., Hentz, J. G., Baxter, L. C., Hernandez, J. L., & Alexander, G. (2004) · Neurology · doi:10.1212/01.wnl.0000129533.26544.bf · Cited by 231 · see citing works
APOE ε2 is associated with intact cognition but increased Alzheimer pathology in the oldest old
Berlau, D. J., Corrada, M. M., Head, E., & Kawas, C. H. (2009) · Neurology · doi:10.1212/01.wnl.0000343853.00346.a4 · Cited by 185 · see citing works
Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E genotypes
den Heijer, T., Oudkerk, M., Launer, L. J., van Duijn, C. M., Albert Hofman, D., & Breteler, M. M. B. (2002) · Neurology · doi:10.1212/wnl.59.5.746 · Cited by 169 · see citing works
Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype
Moffat, S. D., Szekely, C. A., Zonderman, A. B., Kabani, N. J., & Resnick, S. M. (2000) · Neurology · doi:10.1212/wnl.55.1.134 · Cited by 169 · see citing works
Seshadri, S. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540350068018 · Cited by 163 · see citing works
Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women
Cohen, R. M., Small, C., Lalonde, F. M., Friz, J., & Sunderland, T. (2001) · Neurology · doi:10.1212/wnl.57.12.2223 · Cited by 161 · see citing works
The apolipoprotein E varepsilon2 allele and decline in episodic memory
Wilson, R. S. (2002) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.6.672 · Cited by 161 · see citing works
Apolipoprotein E Phenotype and Cognitive Decline in a Prospective Study of Elderly Community Women
Yaffe, K. S., Cauley, J. A., Sands, L. P., & Browner, W. S. (1997) · Archives of Neurology · doi:10.1001/archneur.1997.00550210044011 · Cited by 143 · see citing works
<i>APOE</i> genotype and cognitive decline in a middle-aged cohort
Blair, C. K., Folsom, A. R., Knopman, D. S., Bray, M. S., Mosley, T. H., & Boerwinkle, E. (2005) · Neurology · doi:10.1212/01.wnl.0000149643.91367.8a · Cited by 143 · see citing works
Apolipoprotein E and Alzheimer disease
Huang, Y. (2006) · Neurology · doi:10.1212/01.wnl.0000192102.41141.9e · Cited by 106 · see citing works
Jak, A. J., Houston, W. S., Nagel, B. J., Corey‐Bloom, J., & Bondi, M. W. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000101340 · Cited by 104 · see citing works
Apolipoprotein E-epsilon 2 and Alzheimer's disease
Lippa, C. F., Smith, T. W., Saunders, A. M., Hulette, C., Pulaski-Salo, D., & Roses, A. D. (1997) · Neurology · doi:10.1212/wnl.48.2.515 · Cited by 77 · see citing works
PENN Biomarker Core of the Alzheimer’s Disease Neuroimaging Initiative
Shaw, L. M. J. (2007) · Neurosignals · doi:10.1159/000109755 · Cited by 51 · see citing works
Bipolar deep brain stimulation permits routine EKG, EEG, and polysomnography
Frysinger, R. C., Quigg, M., & Elias, W. J. (2006) · Neurology · doi:10.1212/01.wnl.0000194272.79084.7e · Cited by 48 · see citing works
Hippocampal sulcal cavities on MRI: Relationship to age and apolipoprotein E genotype
Barboriak, D. P., Doraiswamy, P. M., Krishnan, K., Vidyarthi, S., Sylvester, J., & Charles, H. C. (2000) · Neurology · doi:10.1212/wnl.54.11.2150 · Cited by 39 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Bretsky P, Guralnik JM, Launder L, Albert M, Seeman TE. The role of APOE-e4 in longitudinal cognitive de- cline: MacArthur Studies of Successful Aging. Neurology 2003;60:1077-1081.
- Fischl B, Salat DH, Busa E, et al. Whole brain segmenta- tion: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33:341-355.
- Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, Mintum MA. APOE predicts A but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol 2010;67:122-131.
- Neurology ® Launches Subspecialty Alerts by E-mail! Customize your online journal experience by signing up for e-mail alerts related to your subspecialty or area of interest. Access this free service by visiting http://www.neurology.org/cgi/alerts/etoc or click on the "E-mail Alerts" link on the home page. An extensive list of subspecialties, methods, and study design choices will be available for you to choose from-allowing you priority alerts to cutting-edge research in your field!
Cited by
Sorted by citations
Within-subject template estimation for unbiased longitudinal image analysis
Reuter, M., Schmansky, N. J., Rosas, H. D., & Fischl, B. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.02.084 · Cited by 2,356 · see citing works
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception
Weiner, M. W., Veitch, D. P., Aisen, P. S. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Liu, E., et al. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.05.1769 · Cited by 1,011 · see citing works
Self-citationApolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857 · see citing works
Three dimensions of the amyloid hypothesis: time, space and 'wingmen'
Musiek, E. S., & Holtzman, D. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4018 · Cited by 697 · see citing works
The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception
Weiner, M. W., Veitch, D. P., Aisen, P. S. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Liu, E., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.09.172 · Cited by 477 · see citing works
Self-citationAlzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
Weiner, M. W., Veitch, D. P., Aisen, P. S., Beckett, L. A., Cairns, N. J., Cedarbaum, J., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.11.001 · Cited by 348 · see citing works
Self-citationGenes associated with Alzheimer&#39;s disease: an overview and current status
Giri, M., Lü, Y., & Zhang, M. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s105769 · Cited by 311 · see citing works
Fernández-Calle, R., Konings, S. C., Frontiñán-Rubio, J., García-Revilla, J., Camprubí-Ferrer, L., Svensson, M., Martinson, I., Boza-Serrano, A., Venero, J. L., Nielsen, H. M., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00566-4 · Cited by 278 · see citing works
APOE2 enhances neuroprotection against Alzheimer’s disease through multiple molecular mechanisms
Conejero-Goldberg, C., Gomar, J. J., Bobes-Bascaran, T., Hyde, T. M., Kleinman, J. E., Herman, M. M., Chen, S., Davies, P., & Goldberg, T. E. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.194 · Cited by 199 · see citing works
Understanding the Amyloid Hypothesis in Alzheimer’s Disease
Paroni, G., Bisceglia, P., & Seripa, D. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180802 · Cited by 186 · see citing works
Suri, S., Heise, V., Trachtenberg, A. J., & Mackay, C. E. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.10.010 · Cited by 183 · see citing works
APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: A review
O'Donoghue, M. C., Murphy, S. E., Zamboni, G., Nobre, A. C., & Mackay, C. E. (2018) · Cortex · doi:10.1016/j.cortex.2018.03.025 · Cited by 176 · see citing works
Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease
Zhang, X., Alshakhshir, N., & Zhao, L. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.662242 · Cited by 134 · see citing works
Genetics of Alzheimer’s Disease
Vilatela, M. E. A., López, M., & Yescas, P. (2012) · Archives of Medical Research · doi:10.1016/j.arcmed.2012.10.017 · Cited by 129 · see citing works
Caselli, R. J., & Reiman, E. M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129026 · Cited by 109 · see citing works
APOE alters glucose flux through central carbon pathways in astrocytes
Williams, H. C., Farmer, B. C., Piron, M. A., Walsh, A. E., Bruntz, R. C., Gentry, M. S., Sun, R. C., & Johnson, L. A. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104742 · Cited by 105 · see citing works
Keene, C. D., Cudaback, E., Li, X., Montine, K. S., & Montine, T. J. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.08.002 · Cited by 103 · see citing works
Keeney, J. T.-R., Ibrahimi, S., & Zhao, L. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150348 · Cited by 102 · see citing works
Simon, R., Girod, M., Fonbonne, C., Salvador, A., Clément, Y., Lantéri, P., Amouyel, P., Lambert, J. C., & Lemoine, J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.018861 · Cited by 92 · see citing works
Corlier, F. W., Hafzalla, G. W., Faskowitz, J., Kuller, L. H., Becker, J. T., López, O. L., Thompson, P. M., & Braskie, M. N. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2017.12.027 · Cited by 94 · see citing works
Mulder, S. D., Nielsen, H. M., Blankenstein, M. A., Eikelenboom, P., & Veerhuis, R. (2014) · Glia · doi:10.1002/glia.22619 · Cited by 84 · see citing works
Pharmacogenomics of Alzheimer’s Disease: Novel Therapeutic Strategies for Drug Development
Cacabelos, R., Cacabelos, P., Torrellas, C., Tellado, I., & Carril, J. C. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-0956-8_13 · Cited by 85 · see citing works
Imaging Brain Effects of APOE4 in Cognitively Normal Individuals Across the Lifespan
Fouquet, M., Besson, F. L., Gonneaud, J., Joie, R. L., & Chételat, G. (2014) · Neuropsychology Review · doi:10.1007/s11065-014-9263-8 · Cited by 83 · see citing works
Tomaszewski, N., He, X., Solomon, V. A., Lee, M., Mack, W., Quinn, J., Braskie, M., & Yassine, H. N. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-191017 · Cited by 57 · see citing works
Nasrallah, I. M., Gaussoin, S. A., Pomponio, R., Dolui, S., Erus, G., Wright, C. B., Launer, L. J., Detre, J. A., Wolk, D. A., Davatzikos, C. A., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.0178 · Cited by 74 · see citing works
Hostage, C. A., Choudhury, K. R., Doraiswamy, P. M., Petrella, J. R., & Initiative, A. D. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054483 · Cited by 71 · see citing works
ApoE2 and Alzheimer′s disease: time to take a closer look
Zhao, L., & Wu, L. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.179044 · Cited by 70 · see citing works
Hippocampal Volume Differences Between Healthy Young Apolipoprotein E ε2 and ε4 Carriers
Alexopoulos, P., Richter‐Schmidinger, T., Horn, M., Maus, S., Reichel, M., Sidiropoulos, C., Rhein, C., Lewczuk, P., Doerfler, A., & Kornhuber, J. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110356 · Cited by 69 · see citing works
APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD
Manning, E. N., Barnes, J., Cash, D. M., Bartlett, J. W., Leung, K. K., Sebastien Ourselin, A., Fox, N. C., & Initiative, A. D. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097608 · Cited by 64 · see citing works
Konishi, K., Bhat, V., Banner, H., Poirier, J., Joober, R., & Bohbot, V. D. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00349 · Cited by 63 · see citing works
Long range early diagnosis of Alzheimer's disease using longitudinal MR imaging data
Zhu, Y., Kim, M., Zhu, X., Kaufer, D., & Guorong Wu, A. (2020) · Medical Image Analysis · doi:10.1016/j.media.2020.101825 · Cited by 54 · see citing works
Salvadó, G., Grothe, M. J., Groot, C., Moscoso, A., Schöll, M., Gispert, J. D., Ossenkoppele, R., & Initiative, A. D. N. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05192-8 · Cited by 54 · see citing works
Clinical phenotype, atrophy, and small vessel disease in APOE ε2 carriers with Alzheimer disease
Groot, C., Sudre, C. H., Barkhof, F., Teunissen, C. E., van Berckel, B. N. M., Seo, S. W., Sebastien Ourselin, A., Scheltens, P., Cardoso, M. J., van der Flier, W. M., et al. (2018) · Neurology · doi:10.1212/wnl.0000000000006503 · Cited by 53 · see citing works
Sacuiu, S. F. (2016) · Handbook of clinical neurology · doi:10.1016/b978-0-12-802973-2.00008-2 · Cited by 51 · see citing works
Lupton, M. K., Robinson, G. A., Adam, R. J., Rose, S., Byrne, G. J., Salvado, O., Pachana, N. A., Almeida, O. P., McAloney, K., Gordon, S. D., et al. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102527 · Cited by 47 · see citing works
Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load
Grothe, M. J., Villeneuve, S., Dyrba, M., David Bartrés-faz, A., Wirth, M., Initiative, A. D. N., Initiative, A. D. N., Weiner, M. W., Aisen, P., Weiner, M. W., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003585 · Cited by 47 · see citing works
Self-citationFunction and Comorbidities of Apolipoprotein E in Alzheimer′s Disease
Leduc, V., Domenger, D., Beaumont, L. D., Lalonde, D., Jasmin, S. B., & Poirier, J. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/974361 · Cited by 45 · see citing works
Chen, J., Shu, H., Wang, Z., Liu, D., Shi, Y., Zhang, X., & Zhang, Z. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-141677 · Cited by 41 · see citing works
Apolipoprotein E Genotype e2: Neuroprotection and Its Limits
Kim, H., Devanand, D. P., Carlson, S., & Goldberg, T. E. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.919712 · Cited by 36 · see citing works
Mehta, N. H., Zhou, L., Li, Y., McIntire, L. B., Nordvig, A. S., Butler, T., de Leon, M. J., & Chiang, G. C.-Y. (2023) · Scientific Reports · doi:10.1038/s41598-023-34012-2 · Cited by 39 · see citing works
Self-citationLyall, D. M., Royle, N. A., Harris, S. E., Bastin, M. E., Maniega, S. M., Murray, C. L., Lutz, M. W., Saunders, A. M., Roses, A. D., Hernández, M. C. D. V., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080513 · Cited by 39 · see citing works
Hostage, C. A., Choudhury, K. R., Doraiswamy, P. M., Petrella, J. R., & Initiative, A. D. N. (2014) · Radiology · doi:10.1148/radiol.13131041 · Cited by 34 · see citing works
APOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer’s disease
Brookhouser, N., Raman, S., Frisch, C., Srinivasan, G., & Brafman, D. A. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01076-3 · Cited by 33 · see citing works
APOE and metabolic dysfunction in Alzheimer's disease
(2020) · International Review of Neurobiology · doi:10.1016/bs.irn.2020.02.002 · Cited by 31 · see citing works
Preman, P., Moechars, D., Fertan, E., Wolfs, L., Serneels, L., Shah, D., Lamote, J., Poovathingal, S., Snellinx, A., Mancuso, R., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00162-7 · Cited by 32 · see citing works
Neuroimaging biomarkers for Alzheimer's disease in asymptomatic APOE4 carriers
Chételat, G., & Fouquet, M. (2013) · Revue Neurologique · doi:10.1016/j.neurol.2013.07.025 · Cited by 32 · see citing works
Chiang, G. C.-Y., Insel, P. S., Tosun, D., Schuff, N. W., Truran‐Sacrey, D., Raptentsetsang, S. T., Thompson, P. M., Reiman, E. M., Jack, C. R., Fox, N. C., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.12.010 · Cited by 31 · see citing works
Self-citationDurazzo, T. C., Initiative, A. D. N., Korecka, M., Trojanowski, J. Q., Weiner, M. W., Hara, R. O., Ashford, J. W., & Shaw, L. M. J. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160413 · Cited by 31 · see citing works
Self-citationApolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice
Finch, C. E., & Shams, S. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.07.002 · Cited by 29 · see citing works
Hippocampal and entorhinal cortex volume decline in cognitively intact elderly
Thomann, P. A., Wüstenberg, T., Nolte, H. M., Menzel, P. B., Wolf, R. C., Essig, M., & Schröder, J. (2012) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2012.06.002 · Cited by 30 · see citing works
Are apolipoprotein E fragments a promising new therapeutic target for Alzheimer’s disease?
Vecchio, F. L., Bisceglia, P., Imbimbo, B. P., Lozupone, M., Latino, R. R., Resta, E., Leone, M., Solfrizzi, V., Greco, A., Daniele, A., et al. (2022) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223221081605 · Cited by 28 · see citing works
Durazzo, T. C., Mattsson, N., Weiner, M. W., Korecka, M., Trojanowski, J. Q., & Shaw, L. M. J. (2014) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2014.06.030 · Cited by 28 · see citing works
Self-citationWhite Matter Alterations in Cognitively Normal apoE ɛ2 Carriers: Insight into Alzheimer Resistance?
Chiang, G. C., Zhan, W., Schuff, N., & Weiner, M. W. (2012) · American Journal of Neuroradiology · doi:10.3174/ajnr.a2984 · Cited by 25 · see citing works
Self-citationCerebrospinal fluid biomarkers of Alzheimer’s disease in cognitively healthy elderly
Glodzik, L. (2013) · Frontiers in bioscience · doi:10.2741/4170 · Cited by 23 · see citing works
den Heijer, T., van der Lijn, F., Ikram, M. A., Koudstaal, P. J., van der Lugt, A., Krestin, G. P., Vrooman, H. A., Albert Hofman, D., Niessen, W. J., & Breteler, M. M. B. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.07.005 · Cited by 22 · see citing works
Triebswetter, C., Kiely, M., Khattar, N., Ferrucci, L., Resnick, S., Spencer, R. G., & Bouhrara, M. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.118988 · Cited by 19 · see citing works
Exploring common genetic contributors to neuroprotection from amyloid pathology
Seto, M., Mahoney, E. R., Dumitrescu, L. C., Ramanan, V. K., Engelman, C. D., Deming, Y. K., Albert, M., Johnson, S. C., Zetterberg, H., Blennow, K., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac066 · Cited by 17 · see citing works
Reas, E. T., Triebswetter, C., Banks, S. J., & McEvoy, L. K. (2024) · Alzheimer's Research & Therapy · doi:10.1186/s13195-023-01380-w · Cited by 20 · see citing works
“Although lower amyloid burden has been observed among APOE2 carriers, differences in tau or atrophy have been inconclusive [11, 12], with some reports of slower hippocampal atrophy among APOE2 carriers [13].”
ResultBumber, J. R., Rački, V., Mežnarić, S., Pelčić, G., & Mršić‐Pelčić, J. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14176047 · Cited by 17 · see citing works
Du, L., Zhang, J., Zhao, Y., Shang, M., Guo, L., Han, J., & Initiative, T. A. D. N. (2023) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2023.03.005 · Cited by 15 · see citing works
Lancaster, C. L., Tabet, N., & Rusted, J. M. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.015 · Cited by 15 · see citing works
The effects of sequential treatments on hippocampal volumes in malignant glioma patients
Nolen, S. C., Lee, B., Shantharam, S., Yu, H. J., Su, M., Billimek, J., & Bota, D. A. (2016) · Journal of Neuro-Oncology · doi:10.1007/s11060-016-2188-8 · Cited by 14 · see citing works
Gong, L., Xu, R.-H., Liu, D., Lan, L., Zhang, B., & Zhang, C.-T. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00374 · Cited by 11 · see citing works
González, R., Gomes, I., Gomes, C., Rocha, R., Durães, L., Sousa, P., Figueruelo, M., Rodríguez, M. D. C., Pita, C., Hornero, R., et al. (2020) · Genes · doi:10.3390/genes12010004 · Cited by 13 · see citing works
Soldan, A., Wang, J., Pettigrew, C. A., Davatzikos, C. A., Erus, G., Hohman, T. J., Dumitrescu, L. C., Bilgel, M., Resnick, S. M., Rivera‐Rivera, L. A., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae276 · Cited by 10 · see citing works
Holden, S. J., Kundu, P., Torres, E. R. S., Sudhakar, R., Krenik, D., Grygoryev, D., Turker, M. S., & Raber, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.767558 · Cited by 10 · see citing works
APOE ε2 and presymptomatic stage Alzheimer disease
Caselli, R. J., & Dueck, A. C. (2010) · Neurology · doi:10.1212/wnl.0b013e3181ff94f7 · Cited by 7 · see citing works
Im, Y., Kang, S. H., Park, G., Yoo, H., Chun, M. Y., Kim, C., Park, C. J., Kim, J. P., Jang, H., Kim, H. J., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae213 · Cited by 6 · see citing works
Kim, R. T., Zhou, L., Li, Y., Krieger, A. C., Nordvig, A. S., Butler, T., de Leon, M. J., & Chiang, G. C.-Y. (2024) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2024.122927 · Cited by 6 · see citing works
Self-citationBowirrat, A., Yassin, M., Abir, M., Bisharat, B., & Armaly, Z. (2012) · InTech eBooks · doi:10.5772/48558 · Cited by 6 · see citing works
Zhang, B., Lin, L., Liu, L., Shen, X., & Wu, S. (2022) · Brain Sciences · doi:10.3390/brainsci12020187 · Cited by 5 · see citing works
Ramirez-Carmona, R. (2016) · Functional Neurology · doi:10.11138/fneur/2016.31.4.257 · Cited by 5 · see citing works
Lacey, C., Paterson, T. S. E., Gawryluk, J. R., & Initiative, A. D. N. (2024) · PLoS ONE · doi:10.1371/journal.pone.0292576 · Cited by 7 · see citing works
Superior short-term memory in APOE ε2 carriers across the age range
Zokaei, N., Alexander G Board, Slavkova, E., Mackay, C. E., Nobre, A. C., & Masud Husain, B. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112918 · Cited by 4 · see citing works
The ABCA7 transporter, brain lipids and Alzheimer’s disease
Soscia, S. J., & Fitzgerald, M. L. (2013) · Clinical Lipidology · doi:10.2217/clp.12.91 · Cited by 3 · see citing works
Update on Dementia. Pathophysiology, Diagnosis, and Treatment. DSM-IV versus DSM-V
Nina-Estrella, R. E. (2017) · Springer eBooks · doi:10.1007/978-3-319-53126-7_34 · Cited by 3 · see citing works
O’Niel, A., Parkins, C. J., Pederson, A., Saltonstall, E., Bunnell, E., Aggarwal, R., Sandholm, P., Kessler, K., Harrison, H. F., Smith, J. R., et al. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1600119 · Cited by 2 · see citing works
Apolipoprotein E (APOE) Isoforms and Neurobiology of Sporadic Alzheimer’s Disease
Mollica, A., Berardino, G., Bellomo, A., Altamura, M., Panza, F., & Lozupone, M. (2024) · Springer eBooks · doi:10.1007/978-3-031-32035-4_155-1 · Cited by 2 · see citing works
The Systematics and Biogeography of Genus Bidens
Abdullah, S., Munir, M., Javed, B., Ahmad, M., Abbasi, B. A., Dawood, S., & Zhang, L. (2025) · Springer eBooks · doi:10.1007/978-981-96-4257-1_1 · Cited by 2 · see citing works
Perturbed Brain Energy Metabolism in Alzheimer’s Disease and Diabetes
Wu, L. (2017) · KU ScholarWorks (University of Kansas) · Cited by 2 · see citing works
Genetic Risk Factors: Their Function and Comorbidities in Alzheimer′s Disease
Hiltunen, M. O., Bertram, L., & Saunders, A. J. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/925362 · Cited by 1 · see citing works
A Survey of Genetic Risk Factors for Alzheimer’s Disease
Kamath, A. (2023) · Journal of Student Research · doi:10.47611/jsrhs.v12i4.5246 · Cited by 1 · see citing works
Anticancer and Antioxidant Activities of Bidens Species
Khair-un-Nisa, & Saboon (2025) · Springer eBooks · doi:10.1007/978-981-96-4257-1_14 · Cited by 1 · see citing works
Functional and Structural MRI in Alzheimer’s Disease: A Multimodal Approach
Grothe, M. J., Bokde, A. L. W., & Teipel, S. J. (2014) · Springer eBooks · doi:10.1007/978-3-642-54542-9_20 · Cited by 1 · see citing works
Alzheimer’s Disease Genomics and Clinical Applications
Lee, T.-S. W., & Sian, M. (2011) · InTech eBooks · doi:10.5772/18773
Sarlus, H. (2015) · Figshare
Chiang, G. C.-Y., Wang, Z., & Schuff, N. W. (2012)
Self-citationZhao, B., Initiative, A. D. N., Ou, Y., Zhang, X.-Y., Fu, Y., & Tan, L. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230761
Arora, R., Rathore, K. S., & Saurabh, S. S. (2024) · International Journal of Pharmaceutical Chemistry and Analysis · doi:10.18231/j.ijpca.2024.019
Apolipoprotein E (APOE) Isoforms and Neurobiology of Sporadic Alzheimer’s Disease
Mollica, A., Berardino, G., Bellomo, A., Altamura, M., Panza, F., & Lozupone, M. (2025) · Springer eBooks · doi:10.1007/978-3-031-73368-0_155
Reas, E. T., Triebswetter, C., Banks, S. J., & McEvoy, L. K. (2024) · Figshare · doi:10.6084/m9.figshare.24987857
Hou, T., Wei, Q., Shi, L., liu, C., Zhu, M., Tian, X., Zhang, H., Tian, N., Liu, K., González‐Ortiz, F., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-11220681/v1
- Authors
- Chiang, G. C., Insel, P. S., Tosun, D., Schuff, N., Truran-Sacrey, D., Raptentsetsang, S. T., Jack, C. R., Aisen, P. S., Petersen, R. C., Weiner, M. W., & Initiative, F. T. A. D. N.
- Affiliations
- San Francisco VA Medical Center (US)
- From the Departments of Radiology (G.C.C., D.T., N.S., M.W.W.) and Neurology (W.J., M.W.W.), University of California, San Francisco; Center for Imaging of Neurodegenerative Diseases (G.C.C., P.S.I., D.T.S., N.S., D.T., S.T.R.), Department of Veterans Affairs Medical Center, San Francisco, CA; Departments of Radiology (C.R.J.) and Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; and Department of Neurosciences (P.S.A.), University of California, San Diego.
- Venue
- Neurology
- Published
- 2010-11-30
- Volume
- 75
- Issue
- 22
- Pages
- 1976-1981
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3014234
- OpenAlex
- W2116808034
- Cited by
- 94
- References
- 32
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 10 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 8 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 9 · 2015: 4 · 2014: 9 · 2013: 7 · 2012: 9
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (U01 AG024904, AG024904)
- Foundation for the National Institutes of Health (P30AG010129, R01‐AG11378, K01 AG030514, U01AG024904, Grant U01 AG024904, AG024904)
- Michael J. Fox Foundation for Parkinson's Research
- Alzheimer's Association (AG010129, U01 AG024904)
- Dana Foundation (P30 AG010129, K01 AG030514, U01 AG024904)
- Amgen
- Bristol-Myers Squibb (U01 AG024904, AG024904)
- Eli Lilly and Company (U01 AG024904, AG024904)
- Pfizer (AG024904, U01 AG024904)
- AstraZeneca
- GlaxoSmithKline
- Novartis
- Baxter International
- F. Hoffmann-La Roche (AG024904, U01 AG024904)
- Mayo Foundation for Medical Education and Research (AG16574)
- Medpace (U01 AG024904)
- Synarc (U01 AG024904, P30 AG010129, K01 AG030514)
- Alzheimer's Disease Neuroimaging Initiative (U01AG024904, AG024904, P30 AG010129, K01 AG030514)
- Northern California Institute for Research and Education (U01 AG024904, K01 AG030514, P30 AG010129)
- University of Oxford
- Dainippon Sumitomo Pharma
- Elan (U01 AG024904)
- Eisai (U01 AG024904, AG024904)
- Astellas Pharma
- Otsuka Pharmaceutical
- Astellas Foundation for Research on Metabolic Disorders
- Mitsubishi Tanabe Pharma Corporation
- National Institutes of Health (5u01ag024904-10, AG11378, U01-AG024904, Grant U01 AG024904, AG010129, AG024904, AG10483, AG16574)
- Genentech (AG024904, U01 AG024904)
- Forest Laboratories
- University of California, Los Angeles
- Allergan
- University of California, San Diego
- Avid Radiopharmaceuticals
- National Institute on Aging (U01-AG-024904, AG 10483, P30AG010129, AG 024904, AG 16574, U01AG006786, K01AG030514, AG010129, R01AG011378, AG-11378, R01AG010897, U19AG010483, P01AG012435, P01AG019724, P50AG023501, P50AG016574)
- National Institute of Biomedical Imaging and Bioengineering (U01 AG024904, T32EB001631, AG024904)
- National Center for Research Resources (P41RR023953)
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- APOE2, hippocampal atrophy, Alzheimer's disease risk, cerebrospinal fluid biomarkers, amyloid-beta, tau protein, phosphorylated tau 181, episodic memory decline, cognitively normal elderly
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Atrophy, Cognition, Female, Genotype, Hippocampus, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Phosphorylation, Risk, tau Proteins, Disease Progression, Genetic Predisposition to Disease, Apolipoprotein E2
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
