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Molecular Neurodegeneration

, 4:42

First Online: 24 October 2009Received: 05 July 2009Accepted: 24 October 2009


BackgroundHypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system CNS.

ResultsMice with a null mutation in the low-density lipoprotein receptor LDLR gene as well as C57BL-6J mice fed a high cholesterol diet developed a distinct microvascular pathology in the CNS that differs from cholesterol-induced atherosclerotic disease. Microvessel diameter was increased but microvascular density and length were not consistently affected. Degenerative changes and thickened vascular basement membranes were present ultrastructurally. The observed pathology shares features with the microvascular pathology of Alzheimer-s disease AD, including the presence of string-like vessels. Brain apolipoprotein E levels which have been previously found to be elevated in LDLR- mice were also increased in C57BL-6J mice fed a high cholesterol diet.

ConclusionIn addition to its effects as an inducer of atherosclerosis in medium to large sized arteries, hypercholesterolemia also induces a microvascular pathology in the CNS that shares features of the vascular pathology found in AD. These observations suggest that high cholesterol may induce microvascular disease in a range of CNS disorders including AD.

AbbreviationsAβamyloid β peptide

ADAlzheimer-s disease

APPamyloid precursor protein

ANOVAanalysis of variance

ApoEapolipoprotein E

CNScentral nervous system

HandEhematoxylin and eosin

HCDhigh-cholesterol diet

ICAM-1intracellular adhesion molecule 1

LCDlow-cholesterol diet

LDL-Clow-density lipoprotein cholesterol

LDLRlow density lipoprotein receptor

NFTneurofibrillary tangle

NPneuritic plaque

PBSphosphate buffered saline

SEMstandard error of the mean

TBSTris-buffered saline

TGSTriton X-goat serum.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1326-4-42 contains supplementary material, which is available to authorized users.

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Autor: Sonia Franciosi - Miguel A Gama Sosa - Daniel F English - Elizabeth Oler - Twethida Oung - William GM Janssen - Rita De


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