Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma.

Abstract

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.

• Authors: Braydon L Burgess, Sean A McIsaac, Kathryn E Naus, Jeniffer Y Chan, Gavin H K Tansley, Jing Yang, Fudan Miao, Colin J D Ross, Miranda van Eck, Michael R Hayden, William van Nostrand, Peter St George-Hyslop, David Westaway, Cheryl L Wellington
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 24 Issue 1 Pg. 114-27 (Oct 2006) ISSN: 0969-9961 [Print] United States
• PMID: 16899370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Cholesterol, HDL
• Cholesterol, VLDL
• DNA, Complementary
• Fatty Acids, Nonesterified
• Inflammation Mediators
• Interleukin-6
• Ketones
• Triglycerides
• C-Reactive Protein
• Cholesterol
• Lipase
• Lipoprotein Lipase

Topics

• Alzheimer Disease (metabolism)
• Amyloid (metabolism)
• Amyloid beta-Peptides (blood)
• Amyloid beta-Protein Precursor (biosynthesis, genetics)
• Animals
• Blotting, Western
• C-Reactive Protein (metabolism)
• Cholesterol (blood)
• Cholesterol, HDL (blood)
• Cholesterol, VLDL (blood)
• DNA, Complementary (biosynthesis, genetics)
• Fatty Acids, Nonesterified (blood)
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-6 (blood)
• Ketones (blood)
• Lipase (metabolism)
• Lipoprotein Lipase (metabolism)
• Liver (enzymology)
• Mice
• Mice, Transgenic
• Triglycerides (blood)