Decreased plasma cholesterol levels during aging in transgenic mouse models of Alzheimer's disease.
A large number of studies deals with the association of cholesterol and Abeta levels, however, the results are so far controversial. Whereas some studies report on increased cholesterol levels, other authors refer to an association of decreased peripheral cholesterol and the incidence of Alzheimer's disease. It is also questionable whether plasma cholesterol levels could be used as a predictive biomarker for the incidence of Alzheimer's disease. In the present report, we studied the relationship between these two parameters during aging in different transgenic mouse models of Alzheimer's disease, expressing both mutant human amyloid precursor protein and mutant human presenilin-1. Measurements of plasma cholesterol levels revealed a significant reduction in aged APP/PS1 and APP/PS1ki mice, whereas plasma levels in young and aged control mice remained almost unchanged. Furthermore, statistical analysis revealed a significant negative correlation between plasma cholesterol and brain Abeta42 levels during aging in the mice expressing both APP and PS1.
Wirths
Oliver
O
Department of Psychiatry, University of the Saarland, 66421 Homburg/Saar, Germany. oliver.wirths@uniklinik-saarland.de
Thelen
Karin
K
Breyhan
Henning
H
Luzón-Toro
Berta
B
Hoffmann
Karl-Heinz
KH
Falkai
Peter
P
Lütjohann
Dieter
D
Bayer
Thomas A
TA
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000097:blood* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001923:Brain Chemistry; D002784:Cholesterol / Q000097:blood*; D002849:Chromatography, Gas; D004797:Enzyme-Linked Immunosorbent Assay; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D053764:Presenilin-1; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D002784:Cholesterol