title: Hypercholesterolemia accelerates amyloid β-induced cognitive deficits.
abstract: Hypercholesterolemia is a known risk factor for Alzheimer's disease (AD).             In the present study, we investigated whether diet-induced hypercholesterolemia             affects AD-like pathologies such as amyloid β-peptide (Aβ) deposition, tau pathology,             inflammation and cognitive impairment, using an Aβ25-35-injected AD-like pathological             mouse model. Hypercholesterolemia was induced by providing apolipoprotein E knock             out (Apo E KO) mice with a high-fat diet for 4 weeks prior to Aβ25-35 injection             and for 4 weeks following Aβ25-35 injection, for a total of 8 weeks of treatment.             Our data showed that intracerebroventricular injection of C57BL/6J mice with Aβ25-35             resulted in increased immunoreactivity of Aβ and phosphorylated-tau (p-tau), which             was accompanied by enhanced microglial CD11b-like immunoreactivity in the brain.             Moreover, hypercholesterolemia slightly increased Aβ and p-tau levels and microglial             activation in the vehicle group, while further increasing the Aβ and p-tau levels             and microglial activation in Aβ25-35-injected mice. Consistent with the neuropathological             analysis, hypercholesterolemia resulted in significant spatial learning and memory             deficits in Aβ25-35-injected mice as revealed by water maze testing. Collectively,             these findings demonstrated that hypercholesterolemia accelerated Aβ accumulation             and tau pathology, which was accompanied by microglial activation and subsequent             aggravation of memory impairment induced by Aβ25-35. Thus, we suggest that the             modulation of cholesterol can be used to reduce the risk of developing AD.
authors: Division of Meridian and Structural Medicine, School of Korean                     Medicine, Pusan National University, Yangsan-si, Gyeongsangnam-do 626-870,                     Republic of Korea.
authors: Sun Haeng
authors: SH
authors: Park
authors: Ji Hyun
authors: JH
authors: Kim
authors: Kyung Ha
authors: KH
authors: Choi
authors: Young Jung
authors: YJ
authors: Jang
authors: Sun Sik
authors: SS
authors: Bae
authors: Byung Tae
authors: BT
authors: Choi
authors: Hwa Kyoung
authors: HK
authors: Shin
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D039481:CD11b Antigen / Q000276:immunology; D002784:Cholesterol / Q000097:blood; D060825:Cognitive Dysfunction / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005247:Feeding Behavior; D006937:Hypercholesterolemia / Q000378:metabolism*; D007249:Inflammation; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D039481:CD11b Antigen; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D002784:Cholesterol