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APOE2 eases cognitive decline during Aging: Clinical and preclinical evaluations
Mitsuru Shinohara1, Takahisa Kanekiyo1, Longyu Yang1
1Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
Annals of Neurology
|March 3, 2016
Summary
The APOE2 gene allele is linked to slower cognitive decline in aging, independent of Alzheimer's pathology. Higher apolipoprotein E (apoE) and cholesterol levels in APOE2 carriers may explain this protective effect.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Apolipoprotein E (apoE) is a key brain cholesterol carrier.
- The APOE4 allele is a significant risk factor for Alzheimer's disease.
- The protective effects of the APOE2 allele are less understood.
Purpose of the Study:
- To clarify the understudied protective effects of the APOE2 gene allele.
- To investigate the association of APOE2 with cognitive decline and brain pathology.
Main Methods:
- Reviewed National Alzheimer's Coordinating Center clinical records.
- Conducted preclinical studies using human apoE-targeted replacement (apoE-TR) mice.
- Assessed cognitive function using water maze tests.
Main Results:
- APOE2 allele associated with less cognitive decline, even with minimal Alzheimer's pathology.
- ApoE2-TR mice showed preserved memory but similar or greater age-related synaptic, inflammatory, and oxidative changes.
- Higher apoE and specific cholesterol levels in apoE2-TR mice correlated with memory performance.
Conclusions:
- APOE2 confers protection against cognitive decline during aging.
- This protection may be independent of amyloid accumulation and neuroinflammation.
- Elevated apoE and altered cholesterol metabolism in APOE2 carriers likely contribute to its beneficial effects.
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