protein
Apolipoprotein A-I
aka Apo-AI, ApoA-I
Gene
APOA1
Organism
Homo sapiens(9606)
Length
267 aa
Mass
30,778 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-1.837
P2
-1.304
S2
not detected
S3
-1.089
Mean log₂FC across detected fractions: -1.4099 (3 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility
Disease associations
Hypoalphalipoproteinemia, primary, 2FHA2
An autosomal recessive disorder of lipoprotein metabolism, biochemically characterized by severe apoA-I deficiency and severely reduced serum high-density lipoprotein cholesterol (HDL-C). Affected individuals have undetectable serum levels of apoA-I, and develop xanthomas and corneal opacities. The disease is generally associated with atherosclerosis and markedly increased cardiovascular risk.
Hypoalphalipoproteinemia, primary, 2, intermediateFHA2I
An autosomal dominant disorder of lipoprotein metabolism, biochemically characterized by partial apoA-I deficiency and reduced serum high-density lipoprotein cholesterol (HDL-C). Affected individuals have half the normal plasma apoA-I and HDL-C levels, and may develop xanthomas and corneal opacities. Most patients do not have increased cardiovascular risk.
Familial apolipoprotein gene cluster deletion syndromeFAPLDS
An autosomal dominant disorder of lipoprotein metabolism. Affected individuals do not produce ApoA-I, ApoC-III and ApoA-IV lipoproteins, have marked plasma high density lipoprotein (HDL) deficiency, and manifest premature atherosclerosis and coronary artery disease.
Amyloidosis, hereditary systemic 3AMYLD3
A form of hereditary systemic amyloidosis, a disorder characterized by amyloid deposition in multiple tissues resulting in a wide clinical spectrum. AMYLD3 clinical features include amyloid neuropathy, nephropathy, hepatopathy, and cardiomyopathy. Inheritance is autosomal dominant.
Sources
Last updated 5/8/2026, 6:31:31 AM