Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model

Lorenzo M. Refolo, Miguel Pappolla, Brian Malester, John LaFrancois, Tara Bryant-Thomas, Rong Wang, G. Stephen Tint, Kumar Sambamurti, Karen Duff

Research output: Contribution to journalArticle

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Abstract

Recent data suggest that cholesterol metabolism is linked to susceptibility to Alzheimer's disease (AD). However, no direct evidence has been reported linking cholesterol metabolism and the pathogenesis of AD. To test the hypothesis that amyloid β-peptide (AB) deposition can be modulated by diet-induced hypercholesterolemia, we used a transgenic-mouse model for AD amyloidosis and examined the effects of a high-fat/high-cholesterol diet on central nervous system (CNS) Aβ accumulation. Our data showed that diet-induced hypercholesterolemia resulted in significantly increased levels of formic acid-extractable Aβ peptides in the CNS. Furthermore, the levels of total Aβ were strongly correlated with the levels of both plasma and CNS total cholesterol. Biochemical analysis revealed that, compared with control, the hypercholesterolemic mice had significantly decreased levels of sAPPα and increased levels of C-terminal fragments (β-CTFs), suggesting alterations in amyloid precursor protein processing in response to hypercholesterolemia. Neuropathological analysis indicated that the hypercholesterolemic diet significantly increased β-amyloid load by increasing both deposit number and size. These data demonstrate that high dietary cholesterol increases Aβ accumulation and accelerates the AD-related pathology observed in this animal model. Thus, we propose that diet can be used to modulate the risk of developing AD. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)321-331
Number of pages11
JournalNeurobiology of Disease
Volume7
Issue number4
DOIs
StatePublished - 2000
Externally publishedYes

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Hypercholesterolemia
Amyloid
Transgenic Mice
Alzheimer Disease
Pathology
Cholesterol
Diet
formic acid
Central Nervous System
Dietary Cholesterol
Peptides
Amyloid beta-Protein Precursor
High Fat Diet
Amyloidosis
Animal Models

ASJC Scopus subject areas

  • Neurology

Cite this

Refolo, L. M., Pappolla, M., Malester, B., LaFrancois, J., Bryant-Thomas, T., Wang, R., ... Duff, K. (2000). Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiology of Disease, 7(4), 321-331. https://doi.org/10.1006/nbdi.2000.0304

Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. / Refolo, Lorenzo M.; Pappolla, Miguel; Malester, Brian; LaFrancois, John; Bryant-Thomas, Tara; Wang, Rong; Tint, G. Stephen; Sambamurti, Kumar; Duff, Karen.

In: Neurobiology of Disease, Vol. 7, No. 4, 2000, p. 321-331.

Research output: Contribution to journalArticle

Refolo, LM, Pappolla, M, Malester, B, LaFrancois, J, Bryant-Thomas, T, Wang, R, Tint, GS, Sambamurti, K & Duff, K 2000, 'Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model', Neurobiology of Disease, vol. 7, no. 4, pp. 321-331. https://doi.org/10.1006/nbdi.2000.0304
Refolo, Lorenzo M. ; Pappolla, Miguel ; Malester, Brian ; LaFrancois, John ; Bryant-Thomas, Tara ; Wang, Rong ; Tint, G. Stephen ; Sambamurti, Kumar ; Duff, Karen. / Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. In: Neurobiology of Disease. 2000 ; Vol. 7, No. 4. pp. 321-331.
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