Apolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease
Abstract
OBJECTIVE: Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. DESIGN: After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. SETTING: University medical center. PATIENTS: At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). MAIN OUTCOME MEASURES: Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. RESULTS: Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. CONCLUSIONS: These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.
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Both cross-sectional and longitudinal PET studies show that nondemented E4 carriers have more hypometabolic regions than controls.
“Moreover, both cross-sectional (21, 22) and longitudinal PET studies (23) show that nondemented E4 carriers have more hypometabolic regions than controls, but a relationship to longitudinally observed decline has not been reported.”
It has been suggested that this association may account for the earlier onset of symptoms in E4 carriers.
“It has been suggested that this association may account for the earlier onset of symptoms in E4 carriers (21–23).”
In a recent study, subjects with the apolipoprotein E e3/e4 genotype, age-associated memory impairment, and a family history of Alzheimer's disease had abnormally low and asymmetric rates of glucose metabolism in a preselected parietal region before the onset of dementia.
“In a recent study, subjects with the apolipoprotein E e 3/ e 4 genotype, age-associated memory impairment, and a family history of Alzheimer's disease had abnormally low and asymmetric rates of glucose metabolism in a preselected parietal region before the onset of dementia.15”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [15]
Case series suggest that abnormalities in glucose metabolism can be detected by PET before substantial impairment occurs in persons at risk for Alzheimer's disease.
“Case series suggest that abnormalities in glucose metabolism can be detected by PET before substantial impairment occurs in persons at risk for Alzheimer's disease [14][15][16]”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [15]
For many subjects with suspected AD or increased risk, what are currently considered downstream biomarker changes potentially precede upstream biomarker changes.
“Our hypothesis, therefore, can accommodate a growing realization that for many subjects with suspected AD, or who have an increased risk of developing AD, what are currently considered downstream biomarker changes potentially precede upstream biomarker changes [206-213].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [210]
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
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
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
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-citationGoate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · see citing works
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
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
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
Phelps, M. E., Huang, S. C., Hoffman, E. J., Selin, C. E., Sokoloff, L., & Kuhl, D. E. (1979) · Annals of Neurology · doi:10.1002/ana.410060502 · Cited by 2,417 · see citing works
MRI-PET Registration with Automated Algorithm
Woods, R. P., Mazziotta, J. C., & Cherry, A. S. R. (1993) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199307000-00004 · Cited by 1,636 · see citing works
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.262.18.2551 · Cited by 1,627 · see citing works
Le test de copie d'une figure complexe
Osterrieth, P. M. (1944) · Medical Entomology and Zoology · Cited by 1,617 · see citing works
Evaluating storage, retention, and retrieval in disordered memory and learning
Buschke, H., & Fuld, P. (1974) · Neurology · doi:10.1212/wnl.24.11.1019 · Cited by 1,614 · see citing works
Brown, A., Brummel‐Smith, K. V., Burgess, L., D’Agostino, R. B., Goldschmidt, J. W., Halter, J. B., Hazzard, W. R., Jahnigen, D. W., Phelps, C. E., Raskind, M. A., et al. (1988) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1988.tb02362.x · Cited by 1,331 · see citing works
The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man.
Reivich, M., Kuhl, D., Wolf, A. P., Greenberg, J. H., Phelps, M. E., Ido, T., Casella, V., Fowler, J. S., Hoffman, E., Alavi, A. A., et al. (1979) · Circulation Research · doi:10.1161/01.res.44.1.127 · Cited by 1,223 · see citing works
The Genetic Defect Causing Familial Alzheimer's Disease Maps on Chromosome 21
George‐Hyslop, P. S., Tanzi, R. E., Polinsky, R. J., Haines, J. L., Nee, L. E., Watkins, P. C., Myers, R. H., Feldman, R. G., Pollen, D. A., Drachman, D. A., et al. (1987) · Science · doi:10.1126/science.2880399 · Cited by 1,160 · see citing works
Apolipoprotein E genotyping by one-stage PCR
Wenham, P. R., Price, W. H., & Blundell, G. (1991) · The Lancet · doi:10.1016/0140-6736(91)92823-k · Cited by 1,070 · see citing works
Genetic Linkage Evidence for a Familial Alzheimer's Disease Locus on Chromosome 14
Schellenberg, G. D., Bird, T. D., Wijsman, E. M., Orr, H. T., Anderson, L., Nemens, E. J., White, J. A., Bonnycastle, L. L., Weber, J. L., Alonso, M. E., et al. (1992) · Science · doi:10.1126/science.1411576 · Cited by 945 · see citing works
Crook, T. H., Bartus, R. T., Ferris, S. H., Whitehouse, P. J., Cohen, G. D., & Gershon, S. (1986) · Developmental Neuropsychology · doi:10.1080/87565648609540348 · Cited by 930 · see citing works
Noninvasive determination of local cerebral metabolic rate of glucose in man
Huang, S. C., Phelps, M. E., Hoffman, E. J., Sideris, K., Selin, C. J., & Kuhl, D. E. (1980) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1980.238.1.e69 · Cited by 926 · see citing works
Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.
(1991) · Europe PMC (PubMed Central) · Cited by 758 · see citing works
Müller‐Gärtner, H. W., Links, J. M., Prince, J. L., Bryan, R. N., McVeigh, E. R., Leal, J. P., Davatzikos, C. A., & Frost, J. J. (1992) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1992.81 · Cited by 756 · see citing works
Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study
Bachman, D. L., Wolf, P. A., Linn, R., Knoefel, J. E., CobbS, J., Belanger, A., D'Agostino, R. B., & White, L. R. (1992) · Neurology · doi:10.1212/wnl.42.1.115 · Cited by 527 · see citing works
Positron Emission Tomography: Human Brain Function and Biochemistry
Phelps, M. E., & Mazziotta, J. C. (1985) · Science · doi:10.1126/science.2860723 · Cited by 471 · see citing works
The Memory Functioning Questionnaire for assessment of memory complaints in adulthood and old age.
Gilewski, M. J., Zelinski, E. M., & Schaie, K. W. (1990) · Psychology and Aging · doi:10.1037//0882-7974.5.4.482 · Cited by 464 · see citing works
Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14
George‐Hyslop, P. S., Haines, J. L., Rogaev, E. I., Mortilla, M., Vaula, G., Pericak‐Vance, M. A., Foncin, J. P., Montesi, M. P., Bruni, A. C., Sorbi, S., et al. (1992) · Nature Genetics · doi:10.1038/ng1292-330 · Cited by 463 · see citing works
The apolipoprotein ε4 allele in patients with Alzheimer's disease
Mayeux, R. P., Stern, Y., Ottman, R., Tatemichi, T. K., Tang, M., Maestre, G. E., Ngai, C. I., Tycko, B., & Ginsberg, H. N. (1993) · Annals of Neurology · doi:10.1002/ana.410340527 · Cited by 414 · see citing works
Temporal Lobe Regions on Magnetic Resonance Imaging Identify Patients With Early Alzheimer's Disease
Killiany, R., Moss, M. B., Albert, M., Sándor, T., Tieman, J., & Jolesz, F. A. (1993) · Archives of Neurology · doi:10.1001/archneur.1993.00540090052010 · Cited by 371 · see citing works
Grady, C. L., Haxby, J. V., Horwitz, B., Sundaram, M., Berg, G., Schapiro, M. B., Friedland, R. P., & Рапопорт, С. И. (1988) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/01688638808402796 · Cited by 357 · see citing works
Psychometric Differentiation of Mild Senile Dementia of the Alzheimer Type
Storandt, M., Botwinick, J., Danziger, W. L., Berg, L., & Hughes, C. P. (1984) · Archives of Neurology · doi:10.1001/archneur.1984.04050170043013 · Cited by 325 · see citing works
The radiologic prediction of Alzheimer disease: the atrophic hippocampal formation.
de Leon, M. J., Golomb, J. B., GEORGE, A. E., Convit, A. J., Tarshish, C. Y., McRae, T., Santi, S. D., Smith, G. S., Ferris, S. H., & Noz, M. E. (1993) · PubMed Central · Cited by 322 · see citing works
Haxby, J. V., Grady, C. L., Koss, E., Horwitz, B., Heston, L. L., Schapiro, M. B., Friedland, R. P., & Rapoport, S. I. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530070043010 · Cited by 310 · see citing works
APOLIPOPROTEIN-E GENOTYPE AND ALZHEIMERS-DISEASE
Hardy, J., Houlden, H., Collinge, J., Kennedy, A. M., Newman, S., Rossor, M. N., Lannfelt, L., Lilius, L., Winblad, B. G., Crook, R., et al. (1993) · UCL Discovery (University College London) · Cited by 286 · see citing works
Quantifying Interictal Metabolic Activity in Human Temporal Lobe Epilepsy
Henry, T. R., Mazziotta, J. C., Engel, J., et al. (1990) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1990.128 · Cited by 181 · see citing works
A quantitative MRI study of vascular dementia
Liu, C.-K., Miller, B. L., Cummings, J. L., Mehringer, C. M., Goldberg, M. A., Howng, S. L., & Benson, D. F. (1992) · Neurology · doi:10.1212/wnl.42.1.138 · Cited by 171 · see citing works
Cerebral glucose metabolic rates in normal human females versus normal males
Baxter, L. R., Mazziotta, J. C., Phelps, M. E., Selin, C. E., Guzé, B. H., & Fairbanks, L. A. (1987) · Psychiatry Research · doi:10.1016/0165-1781(87)90028-x · Cited by 165 · see citing works
Two Roads to Rapid Eye Movement Latency
Kupfer, D. J. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810100087016 · Cited by 140 · see citing works
van Duijn, C. M., & Stijnen, T. (1991) · International Journal of Epidemiology · doi:10.1093/ije/20.supplement_2.s4 · Cited by 124 · see citing works
Distinguishing normal and demented elderly with the selective reminding test
Masur, D. M., Fuld, P. A., Blau, A. D., Thal, L. J., Levin, H. S., & Aronson, M. K. (1989) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/01688638908400920 · Cited by 110 · see citing works
Azari, N. P., Pettigrew, K. D., Schapiro, M. B., Haxby, J. V., Grady, C. L., Pietrini, P., Salerno, J. A., Heston, L. L., Рапопорт, С. И., & Horwitz, B. (1993) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1993.58 · Cited by 104 · see citing works
Cerebral Glucose Metabolic Patterns in Alzheimer's Disease
Small, G. W. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810060047008 · Cited by 90 · see citing works
Self-citationGrady, C. L., Haxby, J. V., Horwitz, B., Gillette, J., Salerno, J. A., Gonzalez-Aviles, A., Carson, R. E., Herscovitch, P., Schapiro, M. B., & Rapoport, S. I. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90018-7 · Cited by 90 · see citing works
Remote, semiautomated production of F-18-labeled 2-deoxy-2-fluoro-D-glucose.
Barrio, J. R., MacDonald, N. S., Robinson, G. D., Najafi, A., Cook, J. S., & Kuhl, D. E. (1981) · PubMed · Cited by 84 · see citing works
Comparability of FDG PET studies in probable Alzheimer's disease.
Herholz, K., Perani, D., Salmon, É., Franck, G., Fazio, F., Heiß, W.-D., & Comar, D. (1993) · PubMed · Cited by 77 · see citing works
Davis, P. C., Gray, L., Albert, M., Wilkinson, W. E., Hughes, J., Heyman, A., Gado, M., Kumar, A. J., Destian, S., Lee, C., et al. (1992) · Neurology · doi:10.1212/wnl.42.9.1676 · Cited by 71 · see citing works
Selective reminding procedure in depression and dementia.
Hart, R. P., Kwentus, J. A., Hamer, R. M., et al. (1987) · Psychology and Aging · doi:10.1037/0882-7974.2.2.111 · Cited by 55 · see citing works
Neuropsychological processes associated with normal aging
van Gorp, W. G., Satz, P., & Mitrushina, M. (1990) · Developmental Neuropsychology · doi:10.1080/87565649009540467 · Cited by 55 · see citing works
Small, G. W., Okonek, A., Mandelkern, M. A., Rue, A. L., Chang, L., Khonsary, A., Ropchan, J., & Blahd, W. H. (1994) · International Psychogeriatrics · doi:10.1017/s1041610294001596 · Cited by 50 · see citing works
Self-citationNonneural Markers in Alzheimer Disease
Blass, J. P., & Gibson, G. E. (1992) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199206040-00003 · Cited by 38 · see citing works
Reliability of drawing regions of interest for positron emission tomographic data
Small, G. W., Stern, C. E., Mandelkern, M. A., Fairbanks, L. A., Min, C. A., & Guzé, B. H. (1992) · Psychiatry Research Neuroimaging · doi:10.1016/0925-4927(92)90025-y · Cited by 22 · see citing works
Self-citationBiologic Markers, Genetics, and Alzheimer's Disease
Small, G. W. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800340073011 · Cited by 11 · see citing works
Self-citation
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Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496 · see citing works
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459 · see citing works
Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease
Minoshima, S., Giordani, B., Berent, S., Frey, K. A., Foster, N. L., & Kuhl, D. E. (1997) · Annals of Neurology · doi:10.1002/ana.410420114 · Cited by 1,802 · 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
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
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
Patterns of Brain Activation in People at Risk for Alzheimer's Disease
Bookheimer, S. Y., Strojwas, M. H., Cohen, M. S., Saunders, A. M., Pericak-Vance, M. A., Mazziotta, J. C., & Small, G. W. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008173430701 · Cited by 1,328 · see citing works
Self-citationFunctional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2635903100 · Cited by 977 · see citing works
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
Mitochondria and Mitochondrial Cascades in Alzheimer’s disease
Swerdlow, R. H. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170585 · Cited by 850 · 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-citationThe Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
The Preclinical Phase of Alzheimer Disease: A 22-Year Prospective Study of the Framingham Cohort
Elias, M. F., Beiser, A., Wolf, P. A., Au, R., White, R. F., & D'Agostino, R. B. (2000) · Archives of Neurology · doi:10.1001/archneur.57.6.808 · Cited by 716 · see citing works
APOLIPOPROTEIN E ALLELES AS RISK FACTORS IN ALZHEIMER'S DISEASE
Roses, M. D. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.387 · Cited by 707 · see citing works
de Leon, M. J., Convit, A., Wolf, O. T., Tarshish, C. Y., DeSanti, S., Rusinek, H., Tsui, W., Kandil, E., Scherer, A. J., Roche, A., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191044198 · Cited by 629 · see citing works
Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications
Bubber, P., Haroutunian, V., Fisch, G., Blass, J. P., & Gibson, G. E. (2005) · Annals of Neurology · doi:10.1002/ana.20474 · Cited by 622 · see citing works
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
Hippocampal formation glucose metabolism and volume losses in MCI and AD
De Santi, S., de Leon, M. J., Rusinek, H., Convit, A., Tarshish, C. Y., Roche, A., Tsui, W. H., Kandil, E., Boppana, M., Daisley, K., et al. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00230-5 · Cited by 548 · see citing works
MELTZER, C. C. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00194-2 · Cited by 517 · see citing works
Morris, J. C., & Price, J. L. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:2:101 · Cited by 513 · see citing works
Fox, N. C., Crum, W. R., Scahill, R. I., Stevens, J. M., Janssen, J. C., & Rossor, M. N. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05408-3 · Cited by 455 · see citing works
Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future
Petrella, J. R., Coleman, R. E., & Doraiswamy, P. M. (2003) · Radiology · doi:10.1148/radiol.2262011600 · Cited by 427 · 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
Neuroimaging markers for the prediction and early diagnosis of Alzheimer's disease dementia
Ewers, M., Sperling, R. A., Klunk, W. E., Weiner, M. W., & Hampel, H. J. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.05.005 · Cited by 345 · see citing works
Abnormalities of mitochondrial enzymes in Alzheimer disease
Gibson, G. E., Sheu, K.-F. R., & Blass, J. P. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050099 · Cited by 345 · see citing works
(1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.2.165 · Cited by 327 · see citing works
Alzheimer's Disease and Mild Cognitive Impairment
Kelley, B. J., & Petersen, R. C. (2007) · Neurologic Clinics · doi:10.1016/j.ncl.2007.03.008 · Cited by 328 · see citing works
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
Jokeit, H., & Ebner, A.-S. (1999) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.67.1.44 · Cited by 314 · see citing works
Apolipoprotein E4 Impairs Neuronal Insulin Signaling by Trapping Insulin Receptor in the Endosomes
Zhao, N., Liu, C.-C., Van Ingelgom, A. J., Martens, Y. A., Linares, C., Knight, J. A., Painter, M. M., Sullivan, P. M., & Bu, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.003 · Cited by 289 · see citing works
Perry, G. L., Nunomura, A., Hirai, K., Zhu, X., Prez, M. D. F., Ávila, J., Castellani, R. J., Atwood, C., Aliev, G., Sayre, L. M., et al. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01113-9 · Cited by 297 · see citing works
Hariri, A. R., & Weinberger, D. R. (2003) · British Medical Bulletin · doi:10.1093/bmb/65.1.259 · Cited by 299 · see citing works
Are mitochondria critical in the pathogenesis of Alzheimer's disease?
Reddy, P. H., & Beal, M. F. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.03.004 · Cited by 289 · see citing works
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
Ungar, L., Altmann, A., & Greicius, M. D. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9272-x · Cited by 248 · see citing works
Sex, Apolipoprotein E ε4 Status, and Hippocampal Volume in Mild Cognitive Impairment
Fleisher, A. (2005) · Archives of Neurology · doi:10.1001/archneur.62.6.953 · Cited by 256 · see citing works
Brain fluorodeoxyglucose (FDG) PET in dementia
Kato, T., Inui, Y., Nakamura, A., & Ito, K. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.02.003 · Cited by 236 · see citing works
Bondi, M. W., Salmon, D. P., Galasko, D., Thomas, R. G., & Thal, L. J. (1999) · Psychology and Aging · doi:10.1037//0882-7974.14.2.295 · Cited by 235 · see citing works
Petit-Taboué, M. C., Landeau, B., Desson, J. F., Desgranges, B., & Baron, J. C. (1998) · NeuroImage · doi:10.1006/nimg.1997.0318 · Cited by 221 · see citing works
Trivedi, M. A., Schmitz, T. W., Ries, M. L., Torgerson, B. M., Sager, M. A., Hermann, B. P., Asthana, S., & Johnson, S. C. (2006) · BMC Medicine · doi:10.1186/1741-7015-4-1 · Cited by 210 · see citing works
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
The Alzheimer's disease mitochondrial cascade hypothesis: an update
Swerdlow, R. H., & Khan, S. M. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.01.011 · Cited by 206 · see citing works
Early detection of Alzheimer’s disease using neuroimaging
Mosconi, L., Bryś, M., Głodzik-Sobańska, L., Santi, S. D., Rusinek, H., & de Leon, M. J. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.05.016 · Cited by 186 · see citing works
Applications of positron emission tomography (PET) in neurology
Tai, Y., & Piccini, P. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.028175 · Cited by 156 · see citing works
Han, S. D., Houston, W. S., Jak, A. J., Eyler, L. T., Nagel, B. J., Fleisher, A., Brown, G. G., Corey‐Bloom, J., Salmon, D. P., Thal, L. J., et al. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.12.013 · Cited by 151 · see citing works
Caroli, A., & Frisoni, G. B. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.024 · Cited by 146 · 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
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
Impairment of Neocortical Metabolism Predicts Progression in Alzheimer’s Disease
Herholz, K., Nordberg, A. K., Salmon, É., Perani, D., Kessler, J., Mielke, R., Halber, M., Jelić, V., Almkvist, O., Collette, F., et al. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017196 · Cited by 129 · see citing works
Burns, D. K., Alexander, R. C., Welsh-Bohmer, K. A., Culp, M., Chiang, C., O’Neil, J., Evans, R. M., Harrigan, P., Plassman, B. L., Burke, J. R., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00043-0 · Cited by 130 · see citing works
Tartaglia, M. C., Rosen, H. J., & Miller, B. L. (2011) · Neurotherapeutics · doi:10.1007/s13311-010-0012-2 · Cited by 124 · see citing works
Genetic susceptibility to Alzheimer disease
Pericak‐Vance, M. A., & Haines, J. L. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89161-1 · Cited by 125 · see citing works
Estrogen use and brain metabolic change in postmenopausal women
Rasgon, N., Silverman, D. H. S., Siddarth, P., Miller, K. J., Ercoli, L. M., Elman, S., Lavretsky, H., Huang, S. C., Phelps, M. E., & Small, G. W. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.03.003 · Cited by 122 · see citing works
Self-citationDisease modifying therapy for AD?<sup>1</sup>
Golde, T. E. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04211.x · Cited by 117 · see citing works
Genetics of human prefrontal function
Winterer, G., & Goldman, D. A. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00205-4 · Cited by 115 · see citing works
Lindstrom, H. A., Fritsch, T., Petot, G. J., Smyth, K. A., Chen, C. H., Debanne, S. M., Lerner, A. J., & Friedland, R. P. (2004) · Brain and Cognition · doi:10.1016/j.bandc.2004.09.020 · Cited by 109 · see citing works
Blunted Rise in Brain Glucose Levels during Hyperglycemia in Adults with Obesity and T2DM
Hwang, J. J., Jiang, L., Hamza, M., Sanchez Rangel, E., Dai, F., Belfort-DeAguiar, R., Parikh, L., Koo, B. B., Rothman, D. L., Mason, G., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.95913 · Cited by 106 · see citing works
Perfusion abnormalities in prodromal AD
Johnson, K. A., & Albert, M. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00137-8 · Cited by 101 · see citing works
APOE-4 Genotype and Neurophysiological Vulnerability to Alzheimer's and Cognitive Aging
Bookheimer, S. Y., & Burggren, A. C. (2009) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.032408.153625 · Cited by 104 · see citing works
Caselli, R. J., Chen, K., Lee, W., Alexander, G. E., & Reiman, E. M. (2008) · Archives of Neurology · doi:10.1001/archneurol.2008.1 · Cited by 101 · see citing works
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
Preclinical Evidence of Alzheimer Changes
Petrie, E. C., Cross, D. J., Galasko, D. R., Schellenberg, G. D., Raskind, M. A., Peskind, E. R., & Minoshima, S. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.59 · Cited by 101 · see citing works
EEG Alterations in Subjects at High Familial Risk for Alzheimer’s Disease
Пономарева, Н. В., Selesneva, N. D., & Jarikov, G. A. (2003) · Neuropsychobiology · doi:10.1159/000073633 · Cited by 97 · see citing works
The apolipoprotein E gene, attention, and brain function.
Parasuraman, R., Greenwood, P. M., & Sunderland, T. (2002) · Neuropsychology · doi:10.1037/0894-4105.16.2.254 · Cited by 98 · see citing works
Weise, C. M., Chen, K., Chen, Y., Kuang, X., Savage, C. R., & Reiman, E. M. (2018) · NeuroImage: Clinical · doi:10.1016/j.nicl.2018.07.016 · Cited by 96 · 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
Пономарева, Н. В., Коровайцева, Г. И., & Rogaev, E. I. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.12.019 · Cited by 92 · see citing works
Axonal energy metabolism, and the effects in aging and neurodegenerative diseases
Yang, S., Park, J. H., & Lu, H.-C. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00634-3 · Cited by 94 · see citing works
Apolipoprotein E, memory and Alzheimer's disease
Soininen, H. S., & Riekkinen, P. J. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10027-8 · Cited by 91 · see citing works
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
Amyloid load in nondemented brains correlates with APOE e4
Caselli, R. J., Walker, D. G., Sue, L. I., Sabbagh, M. N., & Beach, T. G. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.02.016 · Cited by 83 · see citing works
Iron Deposition Leads to Hyperphosphorylation of Tau and Disruption of Insulin Signaling
Wan, W., Cao, L., Kalionis, B., Murthi, P., Xia, S., & Guan, Y. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00607 · Cited by 84 · see citing works
Alzheimer’s disease and its treatment–yesterday, today, and tomorrow
Kim, A. Y., Jerdi, S. A., MacDonald, R., & Triggle, C. R. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1399121 · Cited by 93 · see citing works
Ohnuma, T., Toda, A., Kimoto, A., Takebayashi, Y., Higashiyama, R. I., Tagata, Y., Ito, M., Ota, T., Shibata, N., & Arai, H. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s95362 · Cited by 81 · see citing works
Brain single photon emission computed tomography findings in depressive pseudodementia patients
Cho, M. J., Lyoo, I. K., Lee, D. W., et al. (2002) · Journal of Affective Disorders · doi:10.1016/s0165-0327(01)00301-9 · Cited by 78 · see citing works
Pihlajamäki, M., & Sperling, R. A. (2009) · Behavioural Neurology · doi:10.1155/2009/276384 · Cited by 102 · see citing works
Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers
Borghesani, P. R., Johnson, L. C., Shelton, A. L., Peskind, E. R., Aylward, E., Schellenberg, G. D., & Cherrier, M. M. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.01.012 · Cited by 68 · see citing works
Neuronal plasticity and stressor toxicity during aging
Brewer, G. J. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00121-2 · Cited by 71 · see citing works
Roses, A. D. (1996) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(96)80098-5 · Cited by 69 · see citing works
Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E polymorphism
Lehtovirta, M., Kuikka, J. T., Helisalmi, S., et al. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.64.6.742 · Cited by 68 · see citing works
Welsh‐Bohmer, K. A., Gearing, M., Saunders, A. M., Roses, A. D., & Mirra, S. (1997) · Annals of Neurology · doi:10.1002/ana.410420308 · Cited by 67 · see citing works
Amyloid imaging: Past, present and future perspectives
Villemagne, V. L. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.01.005 · Cited by 64 · see citing works
Pietrini, P., Alexander, G. E., Furey, M. L., Hampel, H. J., & Guazzelli, M. (2000) · International Journal of Psychophysiology · doi:10.1016/s0167-8760(00)00097-0 · Cited by 61 · see citing works
Meier‐Ruge, W., & Bertoni–Freddari, C. (1996) · Reviews in the Neurosciences · doi:10.1515/revneuro.1996.7.1.1 · Cited by 59 · 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
APOE Genotype and Cerebral Blood Flow in Healthy Young Individuals
Scarmeas, N. (2003) · JAMA · doi:10.1001/jama.290.12.1581 · Cited by 55 · see citing works
Apolipoprotein E ε4 Allele and Whole Brain Atrophy in Late-Onset Alzheimer's Disease
Yasuda, M., Mori, E., Kitagaki, H., Yamashita, H., Hirono, N., Shimada, K., Maeda, K., & Tanaka, C. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.6.779 · Cited by 56 · see citing works
Lehtovirta, M., Laakso, M. P., Frisoni, G. B., & Soininen, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00120-2 · Cited by 55 · see citing works
Frontal Lobe Hypometabolism Predicts Cognitive Decline in Patients With Lacunar Infarcts
Reed, B., Eberling, J. L., Mungas, D., Weiner, M. W., & Jagust, W. J. (2001) · Archives of Neurology · doi:10.1001/archneur.58.3.493 · Cited by 54 · see citing works
Jacobson, M. W., Delis, D. C., Bondi, M. W., et al. (2002) · Neuropsychology · doi:10.1037/0894-4105.16.2.132 · Cited by 52 · see citing works
Triad of Risk for Late Onset Alzheimer’s: Mitochondrial Haplotype, APOE Genotype and Chromosomal Sex
Wang, Y., & Brinton, R. D. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00232 · Cited by 52 · see citing works
The clinical epidemiology of Alzheimer's disease.
Keefover, R. (1996) · Neurologic clinics · doi:10.1016/s0733-8619(05)70260-7 · Cited by 54 · see citing works
Estrogen use and brain metabolic change in older adults. A preliminary report
Rasgon, N., Small, G. W., Siddarth, P., Miller, K. J., Ercoli, L. M., Bookheimer, S. Y., Lavretsky, H., Huang, S. C., Barrio, J. R., & Phelps, M. E. (2001) · Psychiatry Research Neuroimaging · doi:10.1016/s0925-4927(01)00084-1 · Cited by 42 · see citing works
Self-citationJagust, W. J. (2000) · Neurologic Clinics · doi:10.1016/s0733-8619(05)70231-0 · Cited by 43 · see citing works
Hawkins, K. M., Goyal, A. I., & Sergio, L. E. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142079 · Cited by 40 · see citing works
Rapoport, S. I. (2003) · Neurotoxicity Research · doi:10.1007/bf03033167 · Cited by 41 · see citing works
Inferior Temporal Lobe Atrophy and APOE Genotypes in Alzheimer’s Disease
Tanaka, S., Kawamata, J., Shimohama, S., Akaki, H., Akiguchi, I., Kimura, J., & Ueda, K. (1998) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017029 · Cited by 41 · see citing works
Brown, A. M., Sheu, R. K.-F., Mohs, R., Haroutunian, V., & Blass, J. P. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:16:1:41 · Cited by 40 · see citing works
M OLECULAR I MAGING WITH P OSITRON E MISSION T OMOGRAPHY
Phelps, M. E. (2002) · Annual Review of Nuclear and Particle Science · doi:10.1146/annurev.nucl.52.050102.090725 · Cited by 39 · see citing works
- Authors
- Small, G. W.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Small, Gary W.
- ORCID
- Small, Gary W.
- Venue
- JAMA: The Journal of the American Medical Association
- Publisher
- American Medical Association (AMA)
- Published
- 1995-03-22
- Volume
- 273
- Issue
- 12
- Pages
- 942
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2159538597
- Cited by
- 604
- References
- 52
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 12 · 2022: 7 · 2021: 16 · 2020: 15 · 2019: 9 · 2018: 12 · 2017: 15 · 2016: 16 · 2015: 7 · 2014: 14 · 2013: 15 · 2012: 18
- FWCI
- 27.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29mh046424-05)
- National Institute on Aging (AG05 128, AG 10123, P50AG005128, P30AG010123, U24AG021886)
- National Institute of Mental Health (1R29 MH46424)
- 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 › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- APOE ε4, familial Alzheimer's disease, brain glucose metabolism, left-right asymmetry, at-risk relatives, early Alzheimer's disease, neuroimaging biomarkers, genetic risk
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Analysis of Variance, Apolipoproteins E, Brain, Deoxyglucose, Family, Female, Fluorine Radioisotopes, Genotype, Glucose, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Models, Theoretical, Neuropsychological Tests, Risk Factors, Tomography, Emission-Computed, Fluorodeoxyglucose F18, Apolipoprotein E4
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