Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.
Apolipoprotein E (apoE) has been implicated as a risk factor for Alzheimer's disease and in the deposition, fibrillogenesis, and clearance of the amyloid beta-peptide (Abeta). To examine the in vivo interactions between apoE and Abeta deposition, we examined 12-month-old transgenic (tg) mice expressing human amyloid precursor protein (APP) with the V717F mutation (APP(V717F) homozygous) on an APOE null background. Elimination of APOE resulted in a redistribution and alteration in the character of Abeta deposition in homozygous APP(V717F) tg mice, with a dramatic reduction in cortical and dentate gyrus deposition, prominent increase in diffuse CA1 and CA3 deposition, and prevention of the formation of thioflavin-S-positive deposits. These alterations in Abeta deposition were not mediated by significant changes in regional APP expression, low-density lipoprotein receptor-related protein expression, or soluble Abeta levels. Thus, apoE in APP(V717F) tg mice not only affects the amount and form of Abeta deposition, but also the anatomical distribution of diffuse Abeta deposits. The APP(V717F) tg mouse can serve as a model to investigate genetic influences on the vulnerability of specific neuroanatomical regions to Abeta deposition.
Irizarry
M C
MC
Alzheimer Disease Research Unit, Massachusetts General Hospital-East, Charlestown 02129, USA.
Cheung
B S
BS
Rebeck
G W
GW
Paul
S M
SM
Bales
K R
KR
Hyman
B T
BT
D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000494:pharmacology*; D006720:Homozygote; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D010446:Peptide Fragments; D011973:Receptors, LDL