Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma.
Dietary or pharmacological manipulation of plasma lipids markedly influences amyloid deposition in animal models of Alzheimer's Disease (AD). However, it is not known whether baseline plasma lipids in AD models differ from wild-type littermates throughout the natural history of disease. To address this question, we measured plasma total cholesterol and triglyceride levels over time in three transgenic AD mouse models in the absence of dietary or pharmacological treatments. Total cholesterol levels were not significantly different between transgenic and wild-type mice during the development of AD neuropathology in all models tested. In contrast, elevated very-low-density lipoprotein (VLDL) triglyceride levels preceded amyloid deposition in two AD models with abundant plasma A beta. Elevated triglycerides were not accompanied by increased inflammatory markers nor decreased lipase activity, but were associated with a significant 30% increase in VLDL-triglyceride secretion rate. Our results suggest that the presence of A beta in plasma may affect peripheral lipid metabolism early in AD pathogenesis.
Burgess
Braydon L
BL
Department of Pathology and Laboratory Medicine, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.
McIsaac
Sean A
SA
Naus
Kathryn E
KE
Chan
Jeniffer Y
JY
Tansley
Gavin H K
GH
Yang
Jing
J
Miao
Fudan
F
Ross
Colin J D
CJ
van Eck
Miranda
M
Hayden
Michael R
MR
van Nostrand
William
W
St George-Hyslop
Peter
P
Westaway
David
D
Wellington
Cheryl L
CL
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007659:Ketones / Q000097:blood; D008049:Lipase / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D014280:Triglycerides / Q000097:blood*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D018076:DNA, Complementary; D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators; D015850:Interleukin-6; D007659:Ketones; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D008049:Lipase; D008071:Lipoprotein Lipase