Decreased expression of the APOA1-APOC3-APOA4 gene cluster is associated with risk of Alzheimer's disease.
BACKGROUND
Apolipoprotein is genetically associated with the risk of Alzheimer's disease (AD). The APOA1, APOC3, and APOA4 genes are closely linked and located on human chromosome 11. Therefore, this gene cluster may be related to the risk of AD.


METHODS
A total of 147 AD patients and 160 healthy controls were randomly recruited from June 2013 to August 2014. APOA1, APOC3, and APOA4 levels were measured using real-time quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay.


RESULTS
APOA1, APOC3 and APOA4 levels were significantly lower in AD patients than controls (P<0.01). APOA1, APOC3, and APOA4 levels were negatively related with the severities of AD determined by Clinical Dementia Rating scores (P<0.01). APOA1, APOC3, and APOA4 levels showed a negative relation with Montgomery-Åsberg Depression Rating Scale scores and a positive relation with RAND 36-item health-survey scores (P<0.01). There was a decreased trend for levels of APOA1, APOC3, and APOA4 in AD patients.


CONCLUSIONS
Low levels of APOA1, APOC3, and APOA4 are associated with risk of AD. APOA1, APOC3, and APOA4 should be developed as combined drugs for the therapy of AD.
Department of Internal Medicine, Fourth Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Qiao
Q
Lin
Neural Department of Internal Medicine, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Yunpeng
Y
Cao
Department of Anatomy, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Jie
J
Gao
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D053305:Apolipoprotein C-III / Q000097:blood / Q000235:genetics*; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D018384:Oxidative Stress; D010641:Phenotype; D012333:RNA, Messenger / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D011795:Surveys and Questionnaires
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D015415:Biomarkers; D012333:RNA, Messenger; C022205:apolipoprotein A-IV
APOA1–APOC3–APOA4 gene cluster; Alzheimer’s disease; Montgomery–Åsberg Depression Rating Scale; RAND 36-item health survey; enzyme-linked immunosorbent assay; real-time quantitative reverse-transcriptase PCR