APP intracellular domain is increased and soluble Aβ is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease

George, Amee J, Holsinger, R. M. Damian, McLean, Catriona A., Laughton, Katrina M., Beyreuther, Konrad, Evin, Genevieve, Masters, Colin L. and Li, Qiao-Xin (2004) APP intracellular domain is increased and soluble Aβ is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease. Neurobiology of Disease, 16 1: 124-132.


Author George, Amee J
Holsinger, R. M. Damian
McLean, Catriona A.
Laughton, Katrina M.
Beyreuther, Konrad
Evin, Genevieve
Masters, Colin L.
Li, Qiao-Xin
Title APP intracellular domain is increased and soluble Aβ is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease
Journal name Neurobiology of Disease   Check publisher's open access policy
ISSN 0969-9961
Publication date 2004
Sub-type Article (original research)
DOI 10.1016/j.nbd.2004.01.009
Volume 16
Issue 1
Start page 124
End page 132
Total pages 9
Place of publication Orlando, Fla.
Publisher Academic Press
Language eng
Subject 110904 Neurology and Neuromuscular Diseases
Abstract Cholesterol is one of multiple factors, other than familial genetic mutations, that can influence amyloid-β peptide (Aβ) metabolism and accumulation in Alzheimer disease (AD). The effect of a high-cholesterol diet on amyloid precursor protein (APP) processing in brain has not been thoroughly studied. This study was designed to further investigate the role of cholesterol in the production of Aβ and APP intracellular domain (AICD) in 12-month-old Tg2576 transgenic mice. The mice were maintained on a high-cholesterol diet for 6 weeks. We found that diet-induced hypercholesterolemia increased the APP cytosolic fragment AICD and reduced sAPPα in the Tg2576 mice compared to the mice on a control basal diet. In addition, the levels of detergent-extracted Aβ40 were reduced, although no change in guanidine-extracted Aβ levels was observed. Full-length APP, α/βC-terminal fragment (α/βCTF), and β-secretase (BACE) were not different in the cholesterol-fed mice compared to the control diet-fed mice. This study suggests that a high dietary cholesterol in aged mice may not only influence Aβ metabolism, but also regulate the AICD levels. AICD has a proposed role in signal transduction and apoptosis, hence modulation of AICD production could be an alternative mechanism by which cholesterol contributes to AD pathogenesis.
Keyword Alzheimer disease
Transgenic mouse
Aβ amyloid
Amyloid precursor protein
AICD
Cholesterol
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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