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Increased CSF cortisol in AD is a function of APOE genotype
E R Peskind1, C W Wilkinson, E C Petrie
1Mental Illness Research, Education, and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, WA 98108, USA. peskind.elaine@seattle.va.gov
Neurology
|April 26, 2001
Summary
Elevated cortisol levels in Alzheimer's disease (AD) are linked to APOE-epsilon4 allele presence, increasing AD risk. Cortisol concentrations vary by APOE genotype in both AD patients and controls.
Area of Science:
- Neuroscience
- Genetics
- Endocrinology
Background:
- Alzheimer's disease (AD) is associated with increased hypothalamic-pituitary-adrenal (HPA) axis activity and elevated cortisol.
- The apolipoprotein E (APOE)-epsilon4 allele is a known risk factor for AD.
- APOE genotype may influence cortisol levels, particularly in the context of AD.
Purpose of the Study:
- To investigate the relationship between cerebrospinal fluid (CSF) cortisol levels and APOE genotype in individuals with AD and healthy controls.
- To determine if APOE genotype modifies cortisol concentrations in AD.
Main Methods:
- Measurement of CSF cortisol levels in 64 AD subjects and 34 non-demented controls.
- Determination of APOE genotypes (epsilon2, epsilon3, epsilon4) for all participants.
Main Results:
- CSF cortisol was significantly higher in AD subjects compared to controls.
- Cortisol levels varied by APOE genotype in both AD and control groups, with a general trend of higher cortisol with epsilon4 and lower with epsilon2.
- No significant difference in CSF cortisol was observed between AD and control groups within the epsilon3/epsilon4 and epsilon3/epsilon3 genotypes.
Conclusions:
- Higher CSF cortisol concentrations correlate with increased APOE-epsilon4 and decreased APOE-epsilon2 allele frequencies in AD.
- APOE genotype influences HPA axis activity, potentially explaining its role in AD risk.
- The findings suggest a link between HPA axis dysregulation, APOE genotype, and Alzheimer's disease pathogenesis.