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
  • View Affiliations

  • 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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March 2013
Volume 31 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Park SH, Kim JH, Choi KH, Jang YJ, Bae SS, Choi BT and Shin HK: Hypercholesterolemia accelerates amyloid β-induced cognitive deficits. Int J Mol Med 31: 577-582, 2013.
APA
Park, S.H., Kim, J.H., Choi, K.H., Jang, Y.J., Bae, S.S., Choi, B.T., & Shin, H.K. (2013). Hypercholesterolemia accelerates amyloid β-induced cognitive deficits. International Journal of Molecular Medicine, 31, 577-582. https://doi.org/10.3892/ijmm.2013.1233
MLA
Park, S. H., Kim, J. H., Choi, K. H., Jang, Y. J., Bae, S. S., Choi, B. T., Shin, H. K."Hypercholesterolemia accelerates amyloid β-induced cognitive deficits". International Journal of Molecular Medicine 31.3 (2013): 577-582.
Chicago
Park, S. H., Kim, J. H., Choi, K. H., Jang, Y. J., Bae, S. S., Choi, B. T., Shin, H. K."Hypercholesterolemia accelerates amyloid β-induced cognitive deficits". International Journal of Molecular Medicine 31, no. 3 (2013): 577-582. https://doi.org/10.3892/ijmm.2013.1233