Conversion of brain apolipoprotein E to an insoluble form in a mouse model of Alzheimer disease.
A beta deposition in the APPV717F transgenic model of Alzheimer's pathology involves apolipoprotein E (apoE). We measured soluble and insoluble apoE in brain region extracts at an early and late stage of plaque development. The apoE levels in the insoluble fraction were greatly elevated in the hippocampus and cortex of aged transgenic animals but were unchanged in wild type or young APPV717F animals. Soluble apoE levels were unaltered. A beta levels were also measured and a positive correlation between apoE and A beta in the insoluble fraction was observed. ApoE transcription was increased approximately 3-fold in the hippocampus of 17-month-old APPV717F mice, suggesting a region-specific upregulation of apoE transcription in the brains of APPV717F mice to compensate for apoE sequestered with fibrillar A beta.
Naidu
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A
Scios Inc. 820 West Maude Avenue, Sunnyvale, CA 94085, USA.
Catalano
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R
Bales
K
K
Wu
S
S
Paul
S M
SM
Cordell
B
B
D000483:Alleles; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012995:Solubility
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E