• DOI:10.1096/fj.02-0285fje
• Corpus ID: 17813857

Function of β‐amyloid in cholesterol transport: a lead to neurotoxicity

@article{Yao2002FunctionO,
  title={Function of $\beta$‐amyloid in cholesterol transport: a lead to neurotoxicity},
  author={Z X Yao and Vassilios Papadopoulos},
  journal={The FASEB Journal},
  year={2002},
  volume={16}
}

• Z. Yao, V. Papadopoulos
• Published 1 October 2002
• Biology, Chemistry
• The FASEB Journal

Amyloid β‐peptide (Aβ), Aβ precursor protein (APP), apolipoprotein E (apoE), and elevated cholesterol levels have been linked to Alzheimer's disease (AD) pathology. High cholesterol levels increase APP and apoE expression in human NT2 neuron progenitor cells. A cholesterol‐ rich environment also induces processing of APP, leading to the formation of Aβ and Aβ peptide fragments. Using a novel method, we determined that 1) cholesterol binds to Aβ at a‐secretase cleavage site; 2) Aβ17–40 rather than Aβ1–40 prevents cholesterol from binding to apoE; 3) Aβ1–40 inhibits cholesterol from binding to low‐density lipoprotein (LDL), leading to decrease cholesterol influx and intracellular cholesterol levels; 4) the binding of cholesterol to apoE or LDL was abolished completely in presence of Aβ1–42. Increased extracellular free cholesterol levels are toxic to neurons; this toxicity is prevented by specific lipoproteins, such as high‐ density lipoproteins, which maintain their ability to bind cholesterol in the presence of Aβ. We propose that one of the physiological functions of Aβ and APP is to control cholesterol transport. AD is associated with increased Aβ production. High cholesterol levels also lead to overproduction of Aβ. Aβ blocks cholesterol trafficking and changes cholesterol homeostasis leading to neurodegeneration and the onset and/or progression of AD pathology.