Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia

Reiman, Eric M.; Chen, Kewei; Alexander, Gene E.; Caselli, Richard J.; Bandy, Daniel; Osborne, David; Saunders, Ann M.; Hardy, John

doi:10.1073/pnas.2635903100

Cited by 977Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCognitive Abilities and Testing

Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia

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Reiman, Eric M., Chen, Kewei, Alexander, Gene E., Caselli, Richard J., Bandy, Daniel, Osborne, David, Saunders, Ann M., Hardy, John·2004·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.2635903100PMC PMC314177

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Abstract

Fluorodeoxyglucose positron emission tomography (PET) studies have found that patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal cortex. We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E ε4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD. We now consider whether ε4 carriers have these regional brain abnormalities as relatively young adults. Apolipoprotein E genotypes were established in normal volunteers 20–39 years of age. Clinical ratings, neuropsychological tests, magnetic resonance imaging, and PET were performed in 12 ε4 heterozygotes, all with the ε3/ε4 genotype, and 15 noncarriers of the ε4 allele, 12 of whom were individually matched for sex, age, and educational level. An automated algorithm was used to generate an aggregate surface-projection map that compared regional PET measurements in the two groups. The young adult ε4 carriers and noncarriers did not differ significantly in their sex, age, educational level, clinical ratings, or neuropsychological test scores. Like previously studied patients with probable AD and late-middle-aged ε4 carriers, the young ε4 carriers had abnormally low rates of glucose metabolism bilaterally in the posterior cingulate, parietal, temporal, and prefrontal cortex. Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia.

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Human carriers of the APOE ε4 allele experience reduced brain glucose metabolism at a young age (20-39 years old).
“PET studies have also revealed that human carriers of the APOE ε4 allele experience reduced brain glucose metabolism at a young age (20–39 years old) [18].”
From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [18]
The brains of APOE4 carriers display decreased glucose utilization in numerous AD-relevant brain regions, as observed by FDG-PET.
“As shown in previous studies, the brains of APOE4 carriers display decreased glucose utilization in numerous AD-relevant brain regions, as observed by FDG-PET16–18.”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [17]
Both young and old APOE4 carriers display decreased glucose utilization, measured by FDG-PET, in brain regions similar to those seen with AD patients.
“early reports by Reiman and colleagues demonstrated that both young and old APOE4 carriers display decreased glucose utilization, as measured by fluorodeoxyglucose positron emission tomography (FDG-PET), in brain regions similar to those seen with AD patients16–18.”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [17]
Cognitively normal individuals at risk for Alzheimer's disease, including ApoE4 carriers, show reduced cerebral metabolism of glucose.
“Cognitively normal individuals at risk for AD, including those carrying ApoE4, showed reduced cerebral metabolism of glucose (Reiman et al., 2004(Reiman et al., , 2005)).”
From Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention (2018) · cites this paper as Reiman et al., 2004
Perturbed brain energy metabolism is one of the major changes that typically occurs in the preclinical Alzheimer's disease brain.
“One of the major changes that typically occurs in the preclinical AD brain is the perturbed brain energy metabolism.”
From Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention (2018) · cites this paper as Reiman et al., 2004

“Mini-mental state”
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
A rating scale for depression
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
[Japanese version of the Neuropsychiatric Inventory--a scoring system for neuropsychiatric disturbance in dementia patients].
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Special Care Units and Traditional Care in Dementia: Relationship with Behavior, Cognition, Functional Status and Quality of Life - A Review
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,803 · see citing works
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,003 · see citing works
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Co-Planar Stereotaxic Atlas of the Human Brain
Talairach, J., & Tournoux, P. (1988) · Medical Entomology and Zoology · Cited by 11,798 · see citing works
Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Self-citation
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Self-citation
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028 · see citing works
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 · see citing works
Self-citation
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.
Hixson, J., & Vernier, D. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43176-1 · Cited by 2,933 · see citing works
Human Brain Function
Frackowiak, R. S. J. (1997) · Cited by 1,713 · see citing works
Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00056-0 · Cited by 1,656 · see citing works
Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.262.18.2551 · Cited by 1,627 · see citing works
Influence of education and occupation on the incidence of Alzheimer's disease
Stern, Y. (1994) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1994.03510370056032 · Cited by 1,434 · see citing works
Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366 · see citing works
Self-citation
Prevalence of Alzheimer's Disease in a Community Population of Older Persons: Higher Than Previously Reported
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.1989.03430180093036 · Cited by 1,226 · see citing works
A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET.
(1995) · PubMed Central · doi:10.2967/jnumed.120.252510a · Cited by 996 · see citing works
Positron Emission Tomography in Evaluation of Dementia
Silverman, D. H. S., Small, G. W., Chang, C. Y., Lu, C. S., de Aburto, M. A. K., Chen, W., Czernin, J. G., Rapoport, S. I., Pietrini, P., Alexander, G. E., et al. (2001) · JAMA · doi:10.1001/jama.286.17.2120 · Cited by 939 · see citing works
Self-citation
Apolipoprotein E allele–specific antioxidant activity and effects on cytotoxicity by oxidative insults and β–amyloid peptides
Miyata, M., & Smith, J. D. (1996) · Nature Genetics · doi:10.1038/ng0996-55 · Cited by 889 · see citing works
Differential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795 · see citing works
Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease
Small, G. W., Ercoli, L. M., Silverman, D. H. S., Huang, S.-C., Komo, S., Bookheimer, S. Y., Lavretsky, H., Miller, K., Siddarth, P., Rasgon, N. L., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090106797 · Cited by 790 · see citing works
Self-citation
Apolipoprotein E Status as a Predictor of the Development of Alzheimer's Disease in Memory-Impaired Individuals
Petersen, R. C. (1995) · JAMA · doi:10.1001/jama.1995.03520400044042 · Cited by 783 · see citing works
Localization of Neurofibrillary Tangles and Beta-Amyloid Plaques in the Brains of Living Patients With Alzheimer Disease
Shoghi, K. I., Small, G. W., Agdeppa, E. D., Kepe, V., Ercoli, L. M., Siddarth, P., Read, S., Satyamurthy, N., Petrič, A., Huang, S., et al. (2002) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200201000-00004 · Cited by 774 · see citing works
Linguistic Ability in Early Life and Cognitive Function and Alzheimer's Disease in Late Life: Findings From the Nun Study
Snowdon, D. A. (1996) · JAMA · doi:10.1001/jama.1996.03530310034029 · Cited by 696 · see citing works
Perforant pathway changes and the memory impairment of Alzheimer's disease
Hyman, B. T., Van Hoesen, G. W., Kromer, L. J., & Damasio, A. R. (1986) · Annals of Neurology · doi:10.1002/ana.410200406 · Cited by 672 · see citing works
Apolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease
Small, G. W. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520360056039 · Cited by 604 · see citing works
Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported.
Evans, D. A., Funkenstein, H. H., Albert, M., Scherr, P. A., Cook, N. R., Chown, M. J., Hebert, L. E., Hennekens, C. H., & Taylor, J. O. (1989) · PubMed · Cited by 599 · see citing works
Amyloid β-Peptide Impairs Glucose Transport in Hippocampal and Cortical Neurons: Involvement of Membrane Lipid Peroxidation
Mark, R. J., Pang, Z., Geddes, J. W., Uchida, K., & Mattson, M. P. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-03-01046.1997 · Cited by 551 · see citing works
Longitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer’s disease treatment studies
Alexander, G. E., Chen, K., Pietrini, P., Rapoport, S. I., & Reiman, E. M. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.5.738 · Cited by 532 · see citing works
Self-citation
The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations.
Hallman, D. M., Boerwinkle, E., Saha, N., Sandholzer, C., Menzel, H., Csazar, A., & Utermann, G. (1991) · PubMed · Cited by 511 · see citing works
Quantitative cerebral anatomy of the aging human brain
Coffey, C. E., Wilkinson, W. E., Parashos, L., Soady, S. A. R., Sullivan, R. J., Patterson, L. J., Figiel, G. S., Webb, M. C., Spritzer, C. E., & Djang, W. T. (1992) · Neurology · doi:10.1212/wnl.42.3.527 · Cited by 480 · see citing works
Declining brain activity in cognitively normal apolipoprotein E ɛ4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease
Reiman, E. M., Caselli, R. J., Chen, K., Alexander, G. E., Bandy, D., & Frost, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061509598 · Cited by 467 · see citing works
Self-citation
Metabolic Mapping of Functional Activity in the Hypothalamo-Neurohypophysial System of the Rat
Schwartz, W. J., Smith, C. B., Davidsen, L., Savaki, H., Sokoloff, L., Mata, M., Fink, D. J., & Gainer, H. (1979) · Science · doi:10.1126/science.462184 · Cited by 454 · see citing works
Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
(1994) · PubMed Central · Cited by 441 · see citing works
Hypothesis: Microtubule Instability and Paired Helical Filament Formation in the Alzheimer Disease Brain Are Related to Apolipoprotein E Genotype
Strittmatter, W. J., Weisgraber, K. H., Goedert, M., Saunders, A. M., Huang, D., Corder, E. H., Dong, L., Jakes, R., Alberts, M. J., Gilbert, J. R., et al. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1019 · Cited by 433 · see citing works
Self-citation
A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain
Mathis, C. A., Bacskai, B. J., Kajdasz, S. T., McLellan, M. E., Frosch, M. P., Hyman, B. T., Holt, D. P., Wang, Y., Huang, G.-F., Debnath, M. L., et al. (2002) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(01)00734-x · Cited by 404 · see citing works
Distribution of cerebral degeneration in Alzheimer's disease: A clinico-pathological study
Brun, A., & Gustafson, L. (1976) · Archiv f�r Psychiatrie und Nervenkrankheiten · doi:10.1007/bf00367450 · Cited by 397 · see citing works
Effects of Human Aging on Patterns of Local Cerebral Glucose Utilization Determined by the [ 18 F] Fluorodeoxyglucose Method
Kuhl, D. E., Metter, E. J., Riege, W. H., & Phelps, M. E. (1982) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1982.15 · Cited by 338 · see citing works
Association of premorbid intellectual function with cerebral metabolism in Alzheimer's disease: implications for the cognitive reserve hypothesis
(1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.2.165 · Cited by 327 · see citing works
Self-citation
Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease
Ibáñez, V., Pietrini, P., Alexander, G. E., Furey, M. L., Teichberg, D., Rajapakse, J. C., Рапопорт, С. И., Schapiro, M. B., & Horwitz, B. (1998) · Neurology · doi:10.1212/wnl.50.6.1585 · Cited by 322 · see citing works
Self-citation
Level of education and change in cognitive function in a community population of older persons
Evans, D. A., Beckett, L. A., Albert, M., Hebert, L. E., Scherr, P. A., Funkenstein, H. H., & Taylor, J. O. (1993) · Annals of Epidemiology · doi:10.1016/1047-2797(93)90012-s · Cited by 312 · see citing works
Childhood mental ability and dementia
Whalley, L. J., Starr, J. M., Athawes, R. W. B., Hunter, D. C., Pattie, A., & Deary, I. J. (2000) · Neurology · doi:10.1212/wnl.55.10.1455 · Cited by 274 · see citing works
Statement on Use of Apolipoprotein E Testing for Alzheimer Disease
Farrer, L. A. (1995) · JAMA · doi:10.1001/jama.1995.03530200063039 · Cited by 271 · see citing works
Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease
Reiman, E. M., Uecker, A., Caselli, R. J., Lewis, S., Bandy, D., De Leon, M. J., De Santi, S., Convit, A., Osborne, D., Weaver, A., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440226 · Cited by 266 · see citing works
Self-citation
Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: A mechanism to facilitate encoding and circuit maintenance?
Kesslak, J. P., So, V., Choi, J., Cotman, C. W., & Gómez‐Pinilla, F. (1998) · Behavioral Neuroscience · doi:10.1037//0735-7044.112.4.1012 · Cited by 253 · see citing works
Preserved Pontine Glucose Metabolism in Alzheimer Disease: A Reference Region for Functional Brain Image (PET) Analysis
Minoshima, S., Frey, K. A., Foster, N. L., & Kuhl, D. E. (1995) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199507000-00006 · Cited by 252 · see citing works
Noninvasive Quantification of the Cerebral Metabolic Rate for Glucose Using Positron Emission Tomography, 18 F-Fluoro-2-Deoxyglucose, the Patlak Method, and an Image-Derived Input Function
Chen, K., Bandy, D. J., Reiman, E. M., et al. (1998) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199807000-00002 · Cited by 251 · see citing works
Self-citation
Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer's disease
Kennedy, A. M., Frackowiak, R. S. J., Newman, S. K., Bloomfield, P. M., Seaward, J., Roques, P., Lewington, G., Cunningham, V. J., & Rossor, M. N. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11270-7 · Cited by 250 · see citing works
Cellular Bases of Brain Energy Metabolism and Their Relevance to Functional Brain Imaging: Evidence for a Prominent Role of Astrocytes
Magistretti, P. J., & Pellerin, L. (1996) · Cerebral Cortex · doi:10.1093/cercor/6.1.50 · Cited by 243 · see citing works
Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET
Meguro, K., Blaizot, X., Kondoh, Y., Mestric, C. L., Baron, J., & Chavoix, C. (1999) · Brain · doi:10.1093/brain/122.8.1519 · Cited by 228 · see citing works
Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer's disease-related neurofibrillary changes
Ohm, T. G., Müller, H., Braak, H., & Böhl, J. (1995) · Neuroscience · doi:10.1016/0306-4522(95)90397-p · Cited by 222 · see citing works
Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age.
Loessner, A., Alavi, A., Lewandrowski, K., Mozley, D. P., Souder, E., & Gur, R. E. (1995) · PubMed · Cited by 221 · see citing works
Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: A mechanism to facilitate encoding and circuit maintenance?
Kesslak, J. P., So, V., Choi, J. J., et al. (1998) · Behavioral Neuroscience · doi:10.1037/0735-7044.112.4.1012 · Cited by 212 · see citing works
Topography of Cross-sectional and Longitudinal Glucose Metabolic Deficits in Alzheimer's Disease: Pathophysiologic Implications
Smith, G. S. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530350056020 · Cited by 178 · see citing works
High Frequency of Apolipoprotein E ϵ4 Allele in Young Individuals with Very Mild Alzheimer's Disease-Related Neurofibrillary Changes
Ghebremedhin, E., Schultz, C., Braak, E., & Braak, H. (1998) · Experimental Neurology · doi:10.1006/exnr.1998.6860 · Cited by 133 · see citing works
Diminished glucose transport and phosphorylation in Alzheimer's disease determined by dynamic FDG-PET.
Piert, M., Koeppe, R. A., Giordani, B., Berent, S., & KUHL, D. E. (1996) · PubMed · Cited by 131 · see citing works
Clinical Deterioration in Probable Alzheimer's Disease Correlates with Progressive Metabolic Impairment of Association Areas
Mielke, R., Herholz, K., Grond, M., Kessler, J., & Heiß, W.-D. (1994) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106692 · Cited by 121 · see citing works
Statement on use of apolipoprotein E testing for Alzheimer disease. American College of Medical Genetics/American Society of Human Genetics Working Group on ApoE and Alzheimer disease
Farrer, L. A., Brin, M. F., Elsas, L. J., Goate, A., Kennedy, J. L., Mayeux, R. P., Myers, R. H., Reilly, P. M., & RISCH, N. J. (1995) · JAMA · doi:10.1001/jama.274.20.1627 · Cited by 100 · see citing works
18Fluorodeoxyglucose Positron Emission Tomography Studies in Presumed Alzheimer Cases, Including 13 Serial Scans
McGeer, E. G., Peppard, R. P., McGeer, P. L., Tuokko, H., Crockett, D., Parks, R., Akiyama, H., Calne, D. B., Beattie, B. L., & Harrop, R. (1990) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100029930 · Cited by 76 · see citing works
No Difference in Cerebral Glucose Metabolism in Patients With Alzheimer Disease and Differing Apolipoprotein E Genotypes
Corder, E. H., Jelić, V., Basun, H., Lannfelt, L., Valind, S., Winblad, B. G., & Nordberg, A. K. (1997) · Archives of Neurology · doi:10.1001/archneur.1997.00550150035013 · Cited by 65 · see citing works
Decrease of frontal metabolism demonstrated by positron emission tomography in a population of healthy elderly volunteers.
Salmon, É., Maquet, P., Sadzot, B., et al. (1991) · PubMed · Cited by 50 · see citing works
Educational Attainment and Socioeconomic Status of Patients With Autopsy-Confirmed Alzheimer Disease
Muñoz, D. G., Ganapathy, G. R., Eliasziw, M., & Hachinski, V. (2000) · Archives of Neurology · doi:10.1001/archneur.57.1.85 · Cited by 43 · see citing works
Lack of Association of Apolipoprotein E ε4 Allele Dose with Cerebral Glucose Metabolism in Alzheimer Disease
Hirono, N., Mori, E., Yasuda, M., et al. (1998) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199812000-00018 · Cited by 37 · see citing works
Pattern of Cerebral Metabolic Interactions in a Subject with Isolated Amnesia at Risk for Alzheimer's Disease: A Longitudinal Evaluation
Pietrini, P., Azari, N. P., Grady, C. L., Salerno, J. A., Gonzalez-Aviles, A., Heston, L. L., Pettigrew, K. D., Horwitz, B., Haxby, J. V., & Schapiro, M. B. (1993) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000107349 · Cited by 37 · see citing works
Regional cerebral glucose utilization is modulated by the dosage of apolipoprotein E type 4 allele and α1-antichymotrypsin type A allele in Alzheimerʼs disease
Higuchi, M., Arai, H., Nakagawa, T., et al. (1997) · Neuroreport · doi:10.1097/00001756-199708180-00001 · Cited by 31 · see citing works
Apolipoprotein E polymorphism influences the cerebral metabolic pattern in Alzheimer's disease
Mielke, R., Zerres, K., Uhlhaas, S., Kessler, J., & Heiß, W.-D. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00673-9 · Cited by 29 · see citing works
Tracking the decline in cerebral glucose metabolism in persons and laboratory animals at genetic risk for Alzheimer's disease
Reiman, E. M., Caselli, R. J., Alexander, G. E., & Chen, K. (2001) · Clinical Neuroscience Research · doi:10.1016/s1566-2772(01)00006-8 · Cited by 28 · see citing works
Self-citation
Apolipoprotein E and Intellectual Achievement
Caselli, R. J., Hentz, J. G., Osborne, D., Graff‐Radford, N. R., Barbieri, C. J., Alexander, G. E., Hall, G. R., Reiman, E. M., Hardy, J., & Saunders, A. M. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50007.x · Cited by 13 · see citing works
Self-citation
Monte-Carlo based neuroimaging set-level multiple-comparison correction
Chen, K., Reiman, E. M., Bandy, D. J., & Alexander, G. E. (2003) · IFAC Proceedings Volumes · doi:10.1016/s1474-6670(17)33464-x · Cited by 6 · see citing works
Self-citation

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Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155 · see citing works
Self-citation
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · see citing works
Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers
Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396 · see citing works
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Dubois, B., Feldman, H. H., Jacova, C., Hampel, H., Molinuevo, J. L., Blennow, K., DeKosky, S. T., Gauthier, S., Selkoe, D., Bateman, R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70090-0 · Cited by 3,321 · see citing works
Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease
Buckner, R. L., Sepulcre, J., Talukdar, T., Krienen, F. M., Liu, H., Hedden, T., Andrews-Hanna, J. R., Sperling, R. A., & Johnson, K. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5062-08.2009 · Cited by 2,862 · see citing works
Neurodegenerative Diseases Target Large-Scale Human Brain Networks
Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L., & Greicius, M. D. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.024 · Cited by 2,350 · see citing works
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2177-05.2005 · Cited by 2,140 · see citing works
Revising the definition of Alzheimer's disease: a new lexicon
Dubois, B., Feldman, H. H., Jacova, C., Cummings, J. L., DeKosky, S. T., Barberger-Gateau, P., Delacourte, A., Frisoni, G., Fox, N. C., Galasko, D., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70223-4 · Cited by 1,869 · see citing works
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease
Tönnies, E., & Trushina, E. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161088 · Cited by 1,750 · 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
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · see citing works
Ways toward an early diagnosis in Alzheimer’s disease: the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Mueller, S. G., Weiner, M. W., Thal, L. J., Petersen, R. C., Jack, C. R., Jagust, W., Trojanowski, J. Q., Toga, A. W., & Beckett, L. (2005) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2005.06.003 · Cited by 1,233 · see citing works
Biomarker Modeling of Alzheimer’s Disease
Jack, C. R., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.12.003 · Cited by 1,002 · see citing works
Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation
Johnson, E. C. B., Dammer, E. B., Duong, D. M., Ping, L., Zhou, M., Yin, L., Higginbotham, L. A., Guajardo, A., White, B., Troncoso, J. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0815-6 · Cited by 1,001 · see citing works
Self-citation
Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912 · see citing works
Apolipoprotein 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
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 · see citing works
Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease
Reiman, E. M., Chen, K., Liu, X., Bandy, D., Yu, M., Lee, W., Ayutyanont, N., Keppler, J., Reeder, S. A., Langbaum, J. B. S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900345106 · Cited by 785 · see citing works
Self-citation
Alzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672 · see citing works
Function and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Age, APOE and sex: triad of risk of Alzheimer’s disease.
Riedel, B. C., Thompson, P. M., & Brinton, R. D. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.03.012 · Cited by 627 · see citing works
Is Alzheimer’s disease a type 3 diabetes? A critical appraisal
Kandimalla, R., Thirumala, V., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.08.018 · Cited by 621 · see citing works
Imaging the evolution and pathophysiology of Alzheimer disease
Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604 · see citing works
Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons
Liang, W. S., Reiman, E. M., Valla, J., Dunckley, T., Beach, T. G., Grover, A., Niedzielko, T. L., Schneider, L. E., Mastroeni, D., Caselli, R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709259105 · Cited by 585 · see citing works
Self-citation
Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study
Reiman, E. M., Quiroz, Y. T., Fleisher, A. S., Chen, K., Velez-Pardo, C., Jimenez-Del-Rio, M., Fagan, A. M., Shah, A. R., Alvarez, S., Arbelaez, A., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70228-4 · Cited by 541 · see citing works
Self-citation
Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial
Henderson, S. T., Vogel, J. L., Barr, L. J., Garvin, F., Jones, J. J., & Costantini, L. C. (2009) · Nutrition & Metabolism · doi:10.1186/1743-7075-6-31 · Cited by 548 · see citing works
The probabilistic model of Alzheimer disease: the amyloid hypothesis revised
Frisoni, G. B., Altomare, D., Thal, D. R., Ribaldi, F., van der Kant, R., Ossenkoppele, R., Blennow, K., Cummings, J., van Duijn, C., Nilsson, P. M., et al. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00533-w · Cited by 513 · see citing works
Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer's Disease Dementia
Claxton, A., Baker, L. D., Hanson, A., Trittschuh, E. H., Cholerton, B., Morgan, A., Callaghan, M., Arbuckle, M., Behl, C., & Craft, S. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-141791 · Cited by 467 · see citing works
Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle–Aged Adults at Risk for Alzheimer Disease
Willette, A. A., Bendlin, B. B., Starks, E. J., Birdsill, A. C., Johnson, S. C., Christian, B. T., Okonkwo, O. C., La Rue, A., Hermann, B. P., Koscik, R. L., et al. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.0613 · Cited by 418 · see citing works
Episodic memory in normal aging and Alzheimer disease: Insights from imaging and behavioral studies
Tromp, D., Dufour, A., Lithfous, S., Pebayle, T., & Després, O. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.08.006 · Cited by 390 · see citing works
Apolipoprotein e sets the stage: response to injury triggers neuropathology
Mahley, R. W., & Huang, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.11.020 · Cited by 412 · see citing works
Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease
Benzinger, T. L. S., Blazey, T., Jack, C. R., Koeppe, R. A., Su, Y., Xiong, C., Raichle, M. E., Snyder, A. Z., Ances, B. M., Bateman, R. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317918110 · Cited by 391 · see citing works
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372 · see citing works
fMRI 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 · see citing works
Hippocampal hypometabolism predicts cognitive decline from normal aging
Mosconi, L., De Santi, S., Li, J., Tsui, W. H., Li, Y., Boppana, M., Laska, E., Rusinek, H., & de Leon, M. J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.12.008 · Cited by 360 · see citing works
Alzheimer's disease as type 3 diabetes: common pathophysiological mechanisms between Alzheimer's disease and type 2 diabetes
Michailidis, M., Moraitou, D., Tata, D. A., Kalinderi, K., Papamitsou, T., & Papaliagkas, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052687 · Cited by 330 · see citing works
Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity
Chang, S., Ma, T. R., Miranda, R. D., Balestra, M. E., Mahley, R. W., & Huang, Y. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508254102 · Cited by 319 · see citing works
Preclinical Alzheimer disease—the challenges ahead
Sperling, R. A., Karlawish, J., & Johnson, K. A. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.241 · Cited by 291 · see citing works
VDAC1, mitochondrial dysfunction, and Alzheimer’s disease
Shoshan-Barmatz, V., Nahon-Crystal, E., Shteinfer-Kuzmine, A., & Gupta, R. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.010 · Cited by 286 · see citing works
Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Langbaum, J. B. S., Chen, K., Lee, W., Reschke, C., Bandy, D., Fleisher, A. S., Alexander, G. E., Foster, N. L., Weiner, M. W., Koeppe, R. A., et al. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2008.12.072 · Cited by 279 · see citing works
Self-citation
Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease
Cunnane, S. C., Courchesne‐Loyer, A., St‐Pierre, V., Vandenberghe, C., Pierotti, T., Fortier, M., Croteau, E., & Castellano, C. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12999 · Cited by 250 · see citing works
DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial
Stonehouse, W., Conlon, C. A., Podd, J., Hill, S. R., Minihane, A. M., Haskell, C., & Kennedy, D. (2013) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.053371 · Cited by 252 · see citing works
Apolipoprotein E, gender, and Alzheimer’s disease: an overlooked, but potent and promising interaction
Ungar, L., Altmann, A., & Greicius, M. D. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9272-x · Cited by 246 · see citing works
Hypometabolism and Altered Cerebrospinal Fluid Markers in Normal Apolipoprotein E E4 Carriers with Subjective Memory Complaints
Mosconi, L., De Santi, S., Brys, M., Tsui, W. H., Pirraglia, E., Glodzik-Sobanska, L., Rich, K. E., Switalski, R., Mehta, P. D., Pratico, D., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.030 · Cited by 238 · see citing works
Concerted changes in transcripts in the prefrontal cortex precede neuropathology in Alzheimer's disease
Bossers, K., Wirz, K. T. S., Meerhoff, G. F., Essing, A. H. W., van Dongen, J. W., Houba, P., Kruse, C. G., Verhaagen, J., & Swaab, D. F. (2010) · Brain · doi:10.1093/brain/awq258 · Cited by 230 · see citing works
Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism
Mosconi, L., Brys, M., Switalski, R., Mistur, R., Glodzik, L., Pirraglia, E., Tsui, W., De Santi, S., & de Leon, M. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705036104 · Cited by 237 · see citing works
Diabetes is associated with cerebrovascular but not Alzheimer's disease neuropathology
Abner, E. L., Nelson, P. T., Kryscio, R. J., Schmitt, F. A., Fardo, D. W., Woltjer, R. L., Cairns, N. J., Yu, L., Dodge, H. H., Xiong, C., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.12.006 · Cited by 233 · see citing works
Brain FDG PET and the Diagnosis of Dementia
Shivamurthy, V. K. N., Tahari, A. K., Marcus, C., & Subramaniam, R. M. (2015) · American Journal of Roentgenology · doi:10.2214/ajr.13.12363 · Cited by 227 · see citing works
Alzheimer’s disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes
Sekar, S., McDonald, J., Cuyugan, L., Aldrich, J., Kurdoglu, A., Adkins, J., Serrano, G., Beach, T. G., Craig, D. W., Valla, J., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.027 · Cited by 199 · see citing works
Self-citation
Lifespan brain activity, β-amyloid, and Alzheimer's disease
Jagust, W. J., & Mormino, E. C. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.09.004 · Cited by 221 · see citing works
Sex and ApoE Genotype Differences in Treatment Response to Two Doses of Intranasal Insulin in Adults with Mild Cognitive Impairment or Alzheimer's Disease
Claxton, A., Baker, L. D., Wilkinson, C. W., Trittschuh, E. H., Chapman, D., Watson, G. S., Cholerton, B., Plymate, S. R., Arbuckle, M., & Craft, S. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-122308 · Cited by 215 · see citing works
Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups
Fleisher, A. S., Sherzai, A., Taylor, C., Langbaum, J. B. S., Chen, K., & Buxton, R. B. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.06.021 · Cited by 217 · see citing works
Self-citation
Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease
Chen, H.-K., Ji, Z.-S., Dodson, S. E., Miranda, R. D., Rosenblum, C. I., Reynolds, I. J., Freedman, S. B., Weisgraber, K. H., Huang, Y., & Mahley, R. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.151084 · Cited by 209 · see citing works
Temporal lobe functional activity and connectivity in young adult APOE ɛ4 carriers
Dennis, N. A., Browndyke, J. N., Stokes, J., Need, A., Burke, J. R., Welsh‐Bohmer, K. A., & Cabeza, R. (2010) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2009.07.003 · Cited by 201 · see citing works
Metabolomics of Human Brain Aging and Age-Related Neurodegenerative Diseases
Jové, M., Portero-Otín, M., Naudí, A., Ferrer, I., & Pamplona, R. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000091 · Cited by 195 · see citing works
Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention
Wu, L., Zhang, X., & Zhao, L. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.2262-17.2018 · Cited by 185 · see citing works
Aβ-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's disease
Huang, Y. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.04.004 · Cited by 170 · see citing works
Apolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164 · see citing works
Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation
Farmer, B., Kluemper, J., & Johnson, L. (2019) · Cells · doi:10.3390/cells8020182 · Cited by 164 · see citing works
FDG-PET as an independent biomarker for Alzheimer’s biological diagnosis: A longitudinal study
Initiative, O. B. O. A. D. N., Ou, Y.-N., Xu, W., Li, J.-Q., Guo, Y., Cui, M., Chen, K.-L., Huang, Y.-Y., Dong, Q., Tan, L., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0512-1 · Cited by 155 · see citing works
Self-citation
Dementia with Lewy bodies: Basis of cingulate island sign
Graff-Radford, J., Murray, M. E., Lowe, V. J., Boeve, B. F., Ferman, T. J., Przybelski, S. A., Lesnick, T. G., Senjem, M. L., Gunter, J. L., Smith, G. E., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000734 · Cited by 163 · see citing works
Assessment of demographic, genetic, and imaging variables associated with brain resilience and cognitive resilience to pathological tau in patients with Alzheimer disease
Ossenkoppele, R., Lyoo, C. H., Jester-Broms, J., Sudre, C. H., Cho, H., Ryu, Y. H., Choi, J. Y., Smith, R., Strandberg, O., Palmqvist, S., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.5154 · Cited by 161 · see citing works
Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairment
Valla, J., Schneider, L., Niedzielko, T., Coon, K. D., Caselli, R., Sabbagh, M. N., Ahern, G. L., Baxter, L., Alexander, G., Walker, D. G., et al. (2006) · Mitochondrion · doi:10.1016/j.mito.2006.10.004 · Cited by 159 · see citing works
APOE Genotype and Neuroimaging Markers of Alzheimer’s Disease: Systematic Review and Meta-Analysis
Liu, Y., Yu, J.-T., Wang, H.-F., Han, P.-R., Tan, C.-C., Wang, C., Meng, X.-F., Risacher, S. L., Saykin, A. J., & Tan, L. (2015) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-307719 · Cited by 152 · see citing works
The APOE ɛ4 allele modulates brain white matter integrity in healthy adults
Heise, V, Filippini, N., Ebmeier, K. P., & Mackay, C. E. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.90 · Cited by 152 · see citing works
Reduced Posterior Cingulate Mitochondrial Activity in Expired Young Adult Carriers of the APOE ε4 Allele, the Major Late-Onset Alzheimer's Susceptibility Gene
Valla, J., Yaari, R., Wolf, A. B., Kusne, Y., Beach, T. G., Roher, A. E., Corneveaux, J. J., Huentelman, M. J., Caselli, R. J., & Reiman, E. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100129 · Cited by 150 · see citing works
Self-citation
Diabetes drugs in the fight against Alzheimer's disease
Boccardi, V., Murasecco, I., & Mecocci, P. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100936 · Cited by 142 · see citing works
The endosomal-lysosomal pathway is dysregulated by APOE4 expression in vivo
Nuriel, T., Peng, K. Y., Ashok, A., Dillman, A. A., Figueroa, H. Y., Apuzzo, J., Ambat, J., Levy, E., Cookson, M. R., Mathews, P. M., et al. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00702 · Cited by 140 · see citing works
APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls
Sampedro, F., Initiative, F. T. A. D. N., Vilaplana, E., de Leon, M. J., Alcolea, D., Pegueroles, J., Montal, V., Carmona-Iragui, M., Sala, I., Sánchez-Saudinos, M.-B., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5185 · Cited by 135 · see citing works
When Does Alzheimer′s Disease Really Start? The Role of Biomarkers
Lloret, A., Esteve, D., Lloret, M.-A., Cervera-Ferri, A., Lopez, B., Nepomuceno, M., & Monllor, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225536 · Cited by 131 · see citing works
Effects of APOE ‐ε4 allele load on brain morphology in a cohort of middle‐aged healthy individuals with enriched genetic risk for Alzheimer's disease
Cacciaglia, R., Molinuevo, J. L., Falcón, C., Brugulat‐Serrat, A., Sánchez‐Benavides, G., Gramunt, N., Esteller, M., Morán, S., Minguillón, C., Fauria, K., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.016 · Cited by 124 · see citing works
A Mitocentric View of Alzheimer's Disease Suggests Multi-Faceted Treatments
Gibson, G. E., & Shi, Q. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100336 · Cited by 124 · see citing works
Cognitive Performance in Older Women Relative to ApoE-ε4 Genotype and Aerobic Fitness
ETNIER, J. L., CASELLI, R. J., REIMAN, E. M., ALEXANDER, G. E., SIBLEY, B. A., TESSIER, D., & MCLEMORE, E. C. (2007) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000239399.85955.5e · Cited by 124 · see citing works
Self-citation
The Alzheimer’s Prevention Initiative Generation Program: study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer’s disease
Lopez Lopez, C., Tariot, P. N., Caputo, A., Langbaum, J. B., Liu, F., Riviere, M., Langlois, C., Rouzade‐Dominguez, M., Zalesak, M., Hendrix, S., et al. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.02.005 · Cited by 116 · see citing works
Self-citation
Alzheimer's disease including focal presentations
Villain, N., & Dubois, B. (2019) · Seminars in Neurology · doi:10.1055/s-0039-1681041 · Cited by 113 · see citing works
Exercise, APOE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers
Deeny, S. P., Poeppel, D., Zimmerman, J. B., Roth, S. M., Brandauer, J., Witkowski, S., Hearn, J. W., Ludlow, A. T., Contreras-Vidal, J. L., Brandt, J., et al. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2008.02.007 · Cited by 107 · 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
Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function
Orr, A. L., Kim, C., Jimenez-Morales, D., Newton, B. W., Johnson, J. R., Krogan, N. J., Swaney, D. L., & Mahley, R. W. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-181184 · Cited by 103 · see citing works
Hypometabolism in Alzheimer-Affected Brain Regions in Cognitively Healthy Latino Individuals Carrying the Apolipoprotein E ε4 Allele
Langbaum, J. B. S., Chen, K., Caselli, R. J., Lee, W., Reschke, C., Bandy, D., Alexander, G. E., Burns, C. M., Kaszniak, A. W., Reeder, S. A., et al. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.30 · Cited by 100 · see citing works
Self-citation
Cognitive reserve, presynaptic proteins, and dementia in the elderly
Honer, W. G., Barr, A. M., Sawada, K., Thornton, A. E., Morris, M. C., Leurgans, S. E., Schneider, J. A., & Bennett, D. A. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.38 · Cited by 100 · see citing works
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 · see citing works
Genetic Heterogeneity in Alzheimer Disease and Implications for Treatment Strategies
Dominantly Inherited Alzheimer Network, Ringman, J. M., Goate, A., Masters, C. L., Cairns, N. J., Danek, A., Graff-Radford, N., Ghetti, B., & Morris, J. C. (2014) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-014-0499-8 · Cited by 96 · see citing works
Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
Mattsson, N., Groot, C., Jansen, W. J., Landau, S. M., Villemagne, V. L., Engelborghs, S., Mintun, M. M., Lleo, A., Molinuevo, J. L., Jagust, W. J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.009 · Cited by 88 · see citing works
Self-citation
Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes
Mosconi, L., Berti, V., Swerdlow, R. H., Pupi, A., Duara, R., & de Leon, M. (2010) · Human Genomics · doi:10.1186/1479-7364-4-3-170 · Cited by 85 · see citing works
Omega-3 fatty acids and cognitive decline: modulation by ApoEε4 allele and depression
Samieri, C., Féart, C., Proust-Lima, C., Peuchant, E., Dartigues, J.-F., Amieva, H., & Barberger-Gateau, P. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.03.020 · Cited by 84 · see citing works
Telomerase gene therapy ameliorates the effects of neurodegeneration associated to short telomeres in mice
Whittemore, K., Derevyanko, A., Martinez, P., Serrano, R., Pumarola, M., Bosch, F., & Blasco, M. A. (2019) · Aging · doi:10.18632/aging.101982 · Cited by 69 · see citing works
Longitudinal modeling of cognitive aging and the TOMM40 effect
Caselli, R. J., Dueck, A. C., Huentelman, M. J., Lutz, M. W., Saunders, A. M., Reiman, E. M., & Roses, A. D. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.11.006 · Cited by 69 · see citing works
“The posterior cingulate is a brain region that is consistently observed to be hypometabolic with fluorodeoxyglucose positron emission tomography in patients with AD and in asymptomatic APOE e4 carriers, including young adults [24].”
Background
Current understanding of fear learning and memory in humans and animal models and the value of a linguistic approach for analyzing fear learning and memory in humans
Raber, J., Arzy, S., Bertolus, J. B., Depue, B., Haas, H. E., Hofmann, S. G., Kangas, M., Kensinger, E., Lowry, C. A., Marusak, H. A., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.03.015 · Cited by 62 · see citing works
<scp>APOE</scp> genotype affects the pre‐synaptic compartment of glutamatergic nerve terminals
Dumanis, S. B., DiBattista, A. M., Miessau, M., Moussa, C. E. H., & Rebeck, G. W. (2013) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07908.x · Cited by 55 · see citing works
Brief Mindfulness Meditation Induces Gray Matter Changes in a Brain Hub.
Tang, R., Friston, K. J., & Tang, Y.-Y. (2020) · Neural Plasticity · doi:10.1155/2020/8830005 · Cited by 54 · see citing works
Apolipoprotein E as a β-amyloid-independent factor in Alzheimer’s disease
Wolf, A. B., Valla, J., Bu, G., Kim, J., LaDu, M., Reiman, E. M., & Caselli, R. J. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt204 · Cited by 55 · see citing works
Self-citation
APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice
Area-Gomez, E., Larrea, D., Pera, M., Agrawal, R. R., Guilfoyle, D. N., Pirhaji, L., Shannon, K., Arain, H. A., Ashok, A., Chen, Q., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61142-8 · Cited by 55 · see citing works
Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline
Lista, S., Molinuevo, J. L., Cavedo, E., Rami, L., Amouyel, P., Teipel, S. J., Garaci, F., Toschi, N., Habert, M.-O., Blennow, K., et al. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150202 · Cited by 53 · see citing works
Monomeric ß-amyloid interacts with type-1 insulin-like growth factor receptors to provide energy supply to neurons
Giuffrida, M. L., Tomasello, M. F., Pandini, G., Caraci, F., Battaglia, G., Busceti, C., Di Pietro, P., Pappalardo, G., Attanasio, F., Chiechio, S., et al. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00297 · Cited by 52 · see citing works
Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer’s disease models: a systematic review and meta-analysis of preclinical studies
Kong, F., Wu, T., Dai, J., Zhai, Z., Cai, J., Zhu, Z., Xu, Y., & Sun, T. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1205207 · Cited by 54 · see citing works
The relevance of beta-amyloid on markers of Alzheimer’s disease in clinically normal individuals and factors that influence these associations
Mormino, E. C. (2014) · Neuropsychology Review · doi:10.1007/s11065-014-9267-4 · Cited by 44 · see citing works
APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline
Fang, W., Xiao, N., Zeng, G., Bi, D., Dai, X., Mi, X., Ye, Q., Chen, X., & Zhang, J. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01631-0 · Cited by 42 · see citing works
White matter differences between healthy young APOE4 carriers and non-carriers identified with tractography and support vector machines
O'Dwyer, L., Lamberton, F., Matura, S., Scheibe, M., Miller, J., Rujescu, D., Prvulovic, D., & Hampel, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036024 · Cited by 34 · see citing works
Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes
Riviere, M., Langbaum, J. B., Turner, R. S., Rinne, J. O., Sui, Y., Cazorla, P., Ricart, J., Meneses, K., Caputo, A., Tariot, P. N., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13532 · Cited by 28 · see citing works

APOE ε3/ε4 and APOE ε4/ε4 genotypes drive unique gene signatures in the cortex of young micePreprint
Foley, K. E., Garceau, D. T., Kotredes, K. P., Carter, G. W., Sasner, M., & Howell, G. R. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.28.359422 · Cited by 3 · see citing works
Apolipoprotein E Genotype Affects Size of ApoE Complexes in Cerebrospinal Fluid
Heinsinger, N. M., Gachechiladze, M. A., & Rebeck, G. W. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw067 · Cited by 74 · see citing works
[P3–106]: CHASING THE CAUSE OF PLASMA APOE DEFICIENCY IN THE LIVERS OF APOEε4 CARRIERS
Moussaud, S., Brookes, K. J., Ellis, E. C. S., et al. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.06.1317
[The incidence of reversible dementia in 145 patients referred on suspicion of dementia].
Pw, N., Jw, K., Feilberg, J. B., et al. (2002) · PubMed · Cited by 1 · see citing works
APOE Genotype Results in Differential Effects on the Peripheral Clearance of Amyloid-β42 in APOE Knock-in and Knock-out Mice
Sharman, M. J., Morici, M., Hone, E., Berger, T., Taddei, K., Martins, I. J., Lim, W. L. F., Singh, S., Wenk, M. R., Ghiso, J., et al. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100141 · Cited by 54 · see citing works

Authors: Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J.
Affiliations: Mayo Clinic (US)
Translational Genomics Research Institute (US)
National Institutes of Health (US)
ORCID: Reiman, Eric M.
Chen, Kewei
Alexander, Gene E.
Caselli, Richard J.
Saunders, Ann M.
Hardy, John
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2003-12-19
Volume: 101
Issue: 1
Pages: 284-289
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.2635903100
PMC: PMC314177
OpenAlex: W1986144956
Semantic Scholar: eb994dc7b585b491e0b2814b9c41734a99570732
Cited by: 977
References: 72
Citations by year: 2026: 19 · 2025: 19 · 2024: 29 · 2023: 27 · 2022: 37 · 2021: 42 · 2020: 45 · 2019: 47 · 2018: 41 · 2017: 43 · 2016: 40 · 2015: 40 · 2014: 55 · 2013: 55 · 2012: 65
FWCI: 21.42
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)
UCL Discovery (University College London) (submittedVersion)
Funders: National Institute on Aging (P30 AG19610-02, P30AG019610)
National Institute of Mental Health (R01 MH57899-01, R01MH057899)
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: Alzheimer's disease, APOE ε4, genetic risk, brain glucose metabolism, brain abnormalities, young adults, posterior cingulate cortex, prefrontal cortex, parietal cortex, temporal cortex
MeSH terms: Adult, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Female, Glucose, Heterozygote, Humans, Male, Risk Factors, Tomography, Emission-Computed, Case-Control Studies, Apolipoprotein E3, Apolipoprotein E4

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Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia

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