VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment.
BACKGROUND
The expression of vascular endothelial growth factor (VEGF) represents one potential mechanism whereby vascular and Alzheimer's disease (AD) pathologies are related. The authors investigated whether AD cases, especially those having a rapid cognitive decline, more commonly carried a functional promoter gene variant for VEGF (-2578C/A) and showed elevated plasma levels of Vegf. In addition, the authors investigated whether patterns of association also were found for mild cognitive impairment (MCI) and conversion from MCI to AD.


METHODS
Group 1 included 317 AD cases and 320 unaffected control subjects. Group 2 included 113 MCI patients and 130 control subjects. Plasma levels of Vegf were measured by chemiluminescence for a subset of group 1. Genotype determinations were made for all subjects.


RESULTS
The VEGF AA genotype was associated with an increased risk of developing AD (OR = 1.616, p = 0.046). This genotype also was associated with an accelerated cognitive decline in APOE small epsilon4 positive patients with AD (AA vs. CC OR = 6.5, p = 0.04). The VEGF AA genotype was a risk factor for MCI (OR = 2.5, p = 0.037) and MCI conversion to AD in APOE small epsilon4+ (OR = 6.5, CI = 2.014-20.980; p = 0.002). Vegf plasma levels were higher in patients with AD than controls (230 pg/mL vs. 42 pg/mL), and were even higher in those patients with a fast cognitive decline and the APOE epsilon4 allele.


CONCLUSIONS
Modulation of VEGF expression is a potential mechanism associated with the risk of developing AD and its clinical deterioration.
Chiappelli
Martina
M
Department of Experimental Pathology, School of Medicine, University of Bologna, Bologna, Italy.
Borroni
Barbara
B
Archetti
Silvana
S
Calabrese
Elena
E
Corsi
Massimiliano M
MM
Franceschi
Massimo
M
Padovani
Alessandro
A
Licastro
Federico
F
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A