{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:01:16Z","timestamp":1793275276733,"version":"4.5.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,6,7]]},"abstract":"<jats:p>Patients with Alzheimer's disease (AD) have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in regions of the precuneus and the posterior cingulate, parietotemporal, and frontal cortex. Apolipoprotein E (APOE) \u03b54 gene dose (i.e., the number of \u03b54 alleles in a person's APOE genotype) is associated with a higher risk of AD and a younger age at dementia onset. We previously found that cognitively normal late-middle-aged APOE \u03b54 carriers have abnormally low CMRgl in the same brain regions as patients with probable Alzheimer's dementia. In a PET study of 160 cognitively normal subjects 47\u201368 years of age, including 36 \u03b54 homozygotes, 46 heterozygotes, and 78 \u03b54 noncarriers who were individually matched for their gender, age, and educational level, we now find that \u03b54 gene dose is correlated with lower CMRgl in each of these brain regions. This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk.<\/jats:p>","DOI":"10.1073\/pnas.0500579102","type":"journal-article","created":{"date-parts":[[2005,6,2]],"date-time":"2005-06-02T20:25:19Z","timestamp":1117743919000},"page":"8299-8302","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":330,"title":["Correlations between apolipoprotein E \u03b54 gene dose and brain-imaging measurements of regional hypometabolism"],"prefix":"10.1073","volume":"102","author":[{"given":"Eric M.","family":"Reiman","sequence":"first","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Chen","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene E.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Caselli","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bandy","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Osborne","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hardy","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006; Departments of Psychiatry and Radiology, University of Arizona, Tucson, AZ 85724; Departments of Mathematics and Psychology, Arizona State University, Tempe, AZ 85287; Departments of Neurology and Psychology, Mayo Clinic, Scottsdale, AZ 85259; Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC 27710; Department of Neuroscience, Mayo..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,6,2]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.4.636"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.5.738"},{"key":"e_1_3_2_3_2","first-page":"1238","volume":"36","year":"1995","unstructured":"Minoshima, S., Frey, K. A., Koeppe, R. A., Foster, N. L. & Kuhl, D. E. (1995) J. Nucl. Med. 36, 1238-1248.7790950","journal-title":"J. Nucl. Med."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.17.2120"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200103260-00045"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000055847.17752.E6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-003-1194-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3283935"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341202"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-2772(01)00006-8"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2635903100"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03520360056039"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090106797"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)43176-1"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440226"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199807000-00002"},{"key":"e_1_3_2_19_2","unstructured":"Frackowiak R. S. J. Friston K. J. Frith C. D. Dolan R. J. & Mazziotta J. C. (1997) in Human Brain Function (Academic San Diego)."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.6.1585"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11270-7"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061509598"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.154.2.165"},{"key":"e_1_3_2_24_2","unstructured":"Talairach J. & Tournoux P. (1998) in Co-planar Stereotaxic Atlas of the Human Brain (Thieme New York)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0500579102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T13:30:54Z","timestamp":1649770254000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0500579102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,2]]},"references-count":24,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2005,6,7]]}},"alternative-id":["10.1073\/pnas.0500579102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0500579102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,2]]},"assertion":[{"value":"2005-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-06-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}