title: VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment.
abstract: 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.
authors.affiliation: Department of Experimental Pathology, School of Medicine, University of Bologna, Bologna, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Chiappelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Elena
authors.initials: E
authors.lastname: Calabrese
authors.forename: Massimiliano M
authors.initials: MM
authors.lastname: Corsi
authors.forename: Massimo
authors.initials: M
authors.lastname: Franceschi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Federico
authors.initials: F
authors.lastname: Licastro
mesh_terms: 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*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A