Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease

JAMA. 1995 Mar 22-29;273(12):942-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Analysis of Variance
  • Apolipoprotein E4
  • Apolipoproteins E* / genetics
  • Apolipoproteins E* / physiology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiology
  • Deoxyglucose / analogs & derivatives
  • Family
  • Female
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • Genotype
  • Glucose / metabolism*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Models, Theoretical
  • Neuropsychological Tests
  • Risk Factors
  • Tomography, Emission-Computed


  • Apolipoprotein E4
  • Apolipoproteins E
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • Deoxyglucose
  • Glucose