ApoE and Neurodegenerative Diseases in Aging.

Age and apolipoprotein E (ApoE) are the mightiest risk factors for dementia and cardiovascular diseases, but the underlying mechanisms remain unclear. In human, ApoE has three isoforms, ApoE2, ApoE3, and ApoE4, which are expressed by the polymorphic alleles: ɛ2, ɛ3, and ɛ4. Among the three polymorphic alleles, apoE ε4 is the most risk gene. ApoE is the main ligand for the low-density lipoprotein (LDL) receptor and the LDL receptor-related protein (LRP), functioning as the component of plasma lipoproteins in the transportation of lipids. Physiologically, ApoE is a multifunctional protein with central roles in lipid metabolism; it transports lipids, including cholesterol, through the cerebrospinal fluid (CSF) and plasma. ApoE expression regulation and apoE gene polymorphism have an important connection with neurological or neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, and other diseases.