Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APPsw mice

Takashi Mori, Daniel Paris, Terrence Town, Amyn Mohammed Rojiani, D. Larry Sparks, Anthony Delledonne, Fiona Crawford, Laila I. Abdullah, James A. Humphrey, Dennis W. Dickson, Michael J. Mullan

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

Mounting evidence suggests that cholesterol may contribute to the pathogenesis of Alzheimer disease (AD). We examined whether cholesterol might be present in senile plaques, a hallmark neuropathological feature of AD. We employed 2 different fluorometric-staining techniques (filipin staining and an enzymatic technique) for the determination of cholesterol in brains of postmortem confirmed AD patients and in nondemented, age-matched histopathologically normal controls. AD patient brains showed abnormal accumulation of cholesterol in congophilic/birefringent dense cores of senile plaques that was essentially absent in histopathologically normal controls. To determine whether increased senile plaque-associated cholesterol occurred generally in all plaques or was restricted to a specific subset, quantitative analysis was performed. Data indicate abnormal accumulation of cholesterol in cores of mature plaques but not in diffuse or immature plaques. Additionally, transgenic mice that overexpress the "Swedish" amyloid precursor protein (Tg APPsw, line 2576) exhibited a similar pattern of abnormal cholesterol accumulation in mature, congophilic amyloid plaques at 24 months of age that was absent in their control littermates or in 8-month-old Tg APPsw mice (an age prior to amyloid deposition). Taken together, our results imply a link between cholesterol and AD pathogenesis and suggest that cholesterol plays an important role in the formation and/or progression of senile plaques.

Original languageEnglish (US)
Pages (from-to)778-785
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume60
Issue number8
DOIs
StatePublished - Jan 1 2001

Keywords

  • Alzheimer disease
  • Cholesterol
  • Senile plaque
  • Transgenic mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Mori, T., Paris, D., Town, T., Rojiani, A. M., Sparks, D. L., Delledonne, A., Crawford, F., Abdullah, L. I., Humphrey, J. A., Dickson, D. W., & Mullan, M. J. (2001). Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APPsw mice. Journal of Neuropathology and Experimental Neurology, 60(8), 778-785. https://doi.org/10.1093/jnen/60.8.778