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Human apolipoprotein E4 accelerates beta-amyloid deposition in APPsw transgenic mouse brain
D B Carter1, E Dunn, D D McKinley
1Pharmacia Corporation, Kalamazoo, MI 49007, USA. Donald.B.Carter@am.pnu.com
Annals of Neurology
|October 17, 2001
Summary
The apolipoprotein E4 (ApoE4) isoform accelerates amyloid beta deposition in the brain, unlike ApoE3. This finding in transgenic mice supports ApoE4’s role in Alzheimer's disease amyloid plaque formation.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- The apolipoprotein E4 (ApoE4) isoform is a known genetic risk factor for Alzheimer's disease.
- Amyloid plaques, primarily composed of amyloid beta (A beta) peptides, are a hallmark of Alzheimer's pathology.
Purpose of the Study:
- To investigate the differential effects of human apolipoprotein E3 (ApoE3) and ApoE4 isoforms on amyloid plaque formation in a mouse model.
- To determine if ApoE isoforms influence the rate of amyloid beta deposition in the brain.
Main Methods:
- Human ApoE3 or ApoE4 were expressed in transgenic mice carrying the Swedish mutation of human amyloid precursor protein (APPsw).
- Amyloid beta peptide (A beta) levels (A beta40 and A beta42) were quantified using enzyme immunoassay.
- Amyloid plaque formation was assessed via thioflavin-S staining and immunohistochemistry.
Main Results:
- Mice expressing ApoE4 and APPsw exhibited accelerated A beta deposition compared to controls.
- No significant difference in A beta deposition was observed in mice expressing ApoE3 and APPsw.
- Specific quantification of A beta40 and A beta42 confirmed accelerated accumulation in ApoE4-expressing mice.
Conclusions:
- ApoE4 isoform significantly accelerates amyloid beta deposition in the brain relative to the ApoE3 isoform.
- These findings in a transgenic mouse model are consistent with the association of ApoE4 with increased A beta accumulation in human Alzheimer's disease patients.