Role of LDL Cholesterol and Endolysosomes in Amyloidogenesis | 46070

Journal of Neurology & Neurophysiology

ISSN - 2155-9562


Role of LDL Cholesterol and Endolysosomes in Amyloidogenesis and Alzheimer

Xuesong Chen, Liang Hui and Jonathan D Geiger

The pathogenesis of late-onset sporadic Alzheimer’s disease (AD) is believed to result from complex interactions
between nutritional, environmental, epigenetic and genetic factors. Among those factors, altered circulating
cholesterol homeostasis, independent of the APOE genotype, continues to be implicated in brain deposition of
amyloid beta protein (Aβ) and the pathogenesis of AD. It is believed that trafficking of amyloid beta precursor protein
(AβPP) into endolysosomes appears to play a critical role in determining amyloidogenic processing of AβPP
because this is precisely where two enzymes critically important in AβPP metabolism are located; beta amyloid
converting enzyme (BACE-1) and gamma secretase enzyme. We have shown that elevated levels of LDL
cholesterol promote AβPP internalization, disturb neuronal endolysosome structure and function, and increase Aβ
accumulation in neuronal endolysosomes. Here, we will further discuss the linkage between elevated levels of LDL
cholesterol and AD pathogenesis, and explore the underlying mechanisms whereby elevated levels of plasma LDL
cholesterol promote amyloidogenesis.