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March 22, 1995

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

Author Affiliations

From the Departments of Psychiatry and Biobehavioral Sciences (Drs Small, Baxter, La Rue, and Guze, Mr Collins, and Mss Kaplan and Adamson), Neurology (Drs Mazziotta and Chang), Pharmacology (Drs Mazziotta, Baxter, and Phelps), and Radiological Sciences (Dr Mazziotta), the Brain Mapping Division (Dr Mazziotta), and the Alzheimer's Disease Center (Drs Small and Mazziotta), University of California at Los Angeles School of Medicine; the Veterans Affairs Medical Center, West Los Angeles, Calif (Drs Small and Mandelkern); the Department of Physics, University of California, Irvine (Dr Mandelkern); the Department of Psychiatry, University of New Mexico, Albuquerque (Dr La Rue); the Divisions of Neurology and Neurobiology, and the Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC (Drs Corder, Saunders, Pericak-Vance, and Roses); and the Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown (Dr Haines).

JAMA. 1995;273(12):942-947. doi:10.1001/jama.1995.03520360056039

Objective.  —Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 alal- (APOE ε4) is a risk factor for familial AD. To determine if APOE ε4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE ε4 and 19 relatives without APOE ε4. 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 ε4 did not differ from those without APOE ε4 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 ε4 compared with those without APOE ε4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE ε4.

Conclusions.  —These results suggest that the inheritance of APOE ε4 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.(JAMA. 1995;273:942-947)