Apolipoprotein A-I

Apolipoprotein A-I (ApoA-I) is the major structural component of high-density lipoprotein (HDL) particles. It participates in reverse cholesterol transport by promoting cholesterol efflux from tissues and serving as a cofactor for lecithin cholesterol acyltransferase (LCAT), thereby facilitating the return of cholesterol to the liver for excretion (UniProt: P02647). The protein also plays a role in spermatozoa motility as part of the SPAP complex.

Mutations and deletions in APOA1 are associated with several lipid metabolism disorders, including primary hypoalphalipoproteinemia and familial apolipoprotein gene cluster deletion syndrome, which manifest with reduced HDL-C levels, xanthomas, and increased cardiovascular risk (UniProt: P02647). Rare variants have also been linked to hereditary systemic amyloidosis with multi-organ involvement.

In Alzheimer's disease, ApoA-I is significantly downregulated in post-mortem brain tissue from AD patients compared to age-matched controls, with a mean log2 fold-change of −1.41 across multiple subcellular fractions (Chaparral AD proteomics). This reduction may reflect altered lipid metabolism and impaired cholesterol homeostasis in the diseased brain, suggesting a potential protective or structural role for ApoA-I in neurodegeneration.