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Age-related memory decline and apolipoprotein E e4.

Richard J Caselli1

  • 1Department of Neurology, Mayo Clinic, Scottsdale, Arizona 85259, USA. caselli.richard@mayo.edu

Discovery Medicine
|October 1, 2009
PubMed
Summary
This summary is machine-generated.

The APOE epsilon4 allele accelerates memory decline in individuals without Alzheimer's disease (AD) symptoms, suggesting an early, presymptomatic AD stage begins before age 60.

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Area of Science:

  • Neuroscience
  • Genetics
  • Gerontology

Background:

  • The apolipoprotein E (APOE) epsilon4 allele is a significant genetic risk factor for late-onset Alzheimer's disease (AD).
  • Previous research indicates that APOE epsilon4 carriers may experience earlier cognitive changes, but the precise onset and progression in asymptomatic individuals require further elucidation.

Purpose of the Study:

  • To investigate the longitudinal trajectory of memory decline in asymptomatic individuals who carry the APOE epsilon4 allele.
  • To determine if there is an allele-dose effect on memory decline.
  • To establish the age of onset for accelerated memory decline in relation to AD pathology.

Main Methods:

  • Longitudinal assessment of memory function in a cohort of asymptomatic individuals.
  • Genotyping for APOE epsilon4 allele status.
  • Analysis of memory decline rates comparing APOE epsilon4 carriers and non-carriers.
  • Exploration of potential allele-dose effects.

Main Results:

  • Asymptomatic APOE epsilon4 carriers exhibit a significantly accelerated rate of memory decline compared to non-carriers.
  • This accelerated decline appears to begin prior to the age of 60.
  • Evidence suggests a possible allele-dose effect, where individuals with two copies of the APOE epsilon4 allele show a more pronounced decline.

Conclusions:

  • The findings support the existence of a presymptomatic stage of Alzheimer's disease.
  • Accelerated memory decline in APOE epsilon4 carriers before age 60 represents an early biomarker for AD.
  • These results align with neuroimaging and neuropathological data indicating AD-related changes in this age group.