Hypercholesterolemia accelerates amyloid β-induced cognitive deficits

Park,Sun  Haeng; Kim,Ji  Hyun; Choi,Kyung  Ha; Jang,Young  Jung; Bae,Sun  Sik; Choi,Byung  Tae; Shin,Hwa  Kyoung

doi:10.3892/ijmm.2013.1233

Hypercholesterolemia accelerates amyloid β-induced cognitive deficits

Authors:
- Sun Haeng Park
- Ji Hyun Kim
- Kyung Ha Choi
- Young Jung Jang
- Sun Sik Bae
- Byung Tae Choi
- Hwa Kyoung Shin
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Affiliations: Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan-si, Gyeongsangnam-do 626-870, Republic of Korea, Department of Pharmacology, School of Medicine, Pusan National University, Yangsan-si, Gyeongsangnam-do 626-870, Republic of Korea
Published online on: January 8, 2013 https://doi.org/10.3892/ijmm.2013.1233
Pages: 577-582

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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.

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