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APP intracellular domain is increased and soluble Abeta is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease.
Neurobiol Dis. 2004 Jun; 16(1):124-32.ND

Abstract

Cholesterol is one of multiple factors, other than familial genetic mutations, that can influence amyloid-beta peptide (Abeta) 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 Abeta 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 sAPPalpha in the Tg2576 mice compared to the mice on a control basal diet. In addition, the levels of detergent-extracted Abeta40 were reduced, although no change in guanidine-extracted Abeta levels was observed. Full-length APP, alpha/betaC-terminal fragment (alpha/betaCTF), and beta-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 Abeta 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.

Authors+Show Affiliations

Department of Pathology, The University of Melbourne, Victoria, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15207269

Citation

George, Amee J., et al. "APP Intracellular Domain Is Increased and Soluble Abeta Is Reduced With Diet-induced Hypercholesterolemia in a Transgenic Mouse Model of Alzheimer Disease." Neurobiology of Disease, vol. 16, no. 1, 2004, pp. 124-32.
George AJ, Holsinger RM, McLean CA, et al. APP intracellular domain is increased and soluble Abeta is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease. Neurobiol Dis. 2004;16(1):124-32.
George, A. J., Holsinger, R. M., McLean, C. A., Laughton, K. M., Beyreuther, K., Evin, G., Masters, C. L., & Li, Q. X. (2004). APP intracellular domain is increased and soluble Abeta is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease. Neurobiology of Disease, 16(1), 124-32.
George AJ, et al. APP Intracellular Domain Is Increased and Soluble Abeta Is Reduced With Diet-induced Hypercholesterolemia in a Transgenic Mouse Model of Alzheimer Disease. Neurobiol Dis. 2004;16(1):124-32. PubMed PMID: 15207269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - APP intracellular domain is increased and soluble Abeta is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease. AU - George,Amee J, AU - Holsinger,R M Damian, AU - McLean,Catriona A, AU - Laughton,Katrina M, AU - Beyreuther,Konrad, AU - Evin,Genevieve, AU - Masters,Colin L, AU - Li,Qiao-Xin, PY - 2003/11/17/received PY - 2004/01/04/revised PY - 2004/01/15/accepted PY - 2004/6/23/pubmed PY - 2004/8/19/medline PY - 2004/6/23/entrez SP - 124 EP - 32 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 16 IS - 1 N2 - Cholesterol is one of multiple factors, other than familial genetic mutations, that can influence amyloid-beta peptide (Abeta) 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 Abeta 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 sAPPalpha in the Tg2576 mice compared to the mice on a control basal diet. In addition, the levels of detergent-extracted Abeta40 were reduced, although no change in guanidine-extracted Abeta levels was observed. Full-length APP, alpha/betaC-terminal fragment (alpha/betaCTF), and beta-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 Abeta 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. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/15207269/APP_intracellular_domain_is_increased_and_soluble_Abeta_is_reduced_with_diet_induced_hypercholesterolemia_in_a_transgenic_mouse_model_of_Alzheimer_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S096999610400021X DB - PRIME DP - Unbound Medicine ER -