Endolysosome involvement in LDL cholesterol-induced Alzheimer's disease-like pathology in primary cultured neurons.

Life Sciences
Liang HuiJonathan D Geiger

Abstract

Elevated levels of circulating cholesterol are extrinsic factors contributing to the pathogenesis of sporadic Alzheimer's disease (AD). We showed previously that rabbits fed a cholesterol-enriched diet exhibited blood-brain barrier (BBB) dysfunction, increased accumulation of apolipoprotein B (ApoB) in brain neurons, and endolysosomes in brain had disturbed structures and functions. These effects were linked to increased amyloid beta (Aβ) production, increased tau-pathology, and disrupted synaptic integrity. Because pathological changes to endolysosomes represent a very early event in sporadic AD, we determined here the extent to which ApoB-containing LDL cholesterol altered the structure and function of endolysosomes and contributed to the development of AD-like pathology in primary cultured neurons. Cholesterol distribution and endolysosome morphology were determined histologically. Endolysosome pH was measured ratio-metrically with LysoSensor dye. Endolysosome enzyme activity was measured for acid phosphatase, cathepsins B and D, and beta-site APP cleaving enzyme 1 (BACE-1). AD-like pathologies, including increased production of Aβ, increased tau-pathology, and disrupted synaptic integrity were determined using ELISA, immuno...Continue Reading

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Citations

Aug 13, 2013·The International Journal of Neuroscience·Zhiyou CaiLiang-Jun Yan
Mar 1, 2013·Biological Reviews of the Cambridge Philosophical Society·Victor A CortesAttilio Rigotti
Feb 17, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yan YeMin Wu
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Jul 6, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yan YeMin Wu
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Feb 26, 2020·Cancer Reports·Peter HalcrowJonathan D Geiger
Nov 11, 2019·Neurobiology of Disease·Zahra AfghahJonathan D Geiger
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Dec 20, 2014·Molecular Neurodegeneration·Catherine MarquerMarie-Claude Potier
Oct 30, 2021·Life Sciences·Pariya KhodabakhshAbolhassan Ahmadiani

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