Apolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease

Gary W. Small, John C. Mazziotta, Mark T. Collins, Lewis R. Baxter, Michael E. Phelps, Andrea Kaplan, Cara F. Adamson, Barry H. Guze, Linda Chang, Mark A. Mandelkern, Asenath La Rue, Elizabeth H. Corder, Ann M. Saunders, Margaret A. Pericak Vance, Allen D. Roses, Jonathan L. Haines

Research output: Contribution to journalArticlepeer-review

507 Scopus citations


Objective. - Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOEε4) is a risk factor for familial AD. To determine if APOEε4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOEε4 and 19 relatives without APOEε4. 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 APOEε4 did not differ from those without APOEε4 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 mission tomography and fludeoxyglucose F 18. Results. - Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOEε4 compared with those without APOEε4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOEε4. Conclusions. - These results suggest that the inheritance of APOEε4 is associated with reduced cerebral parietal metabolism and increased asymmetry in nondemented 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.

Original languageEnglish (US)
Pages (from-to)942-947
Number of pages6
JournalJAMA: The Journal of the American Medical Association
Issue number12
StatePublished - Mar 22 1995
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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