Low serum VEGF levels are associated with Alzheimer's disease.
OBJECTIVE
As vascular endothelial growth factor (VEGF) determines important neurotrophic and neuroprotective actions, we postulated serum VEGF levels could be abnormally low in patients with Alzheimer's disease (AD).


METHODS
We measured serum VEGF levels (VEGF(165) isoform by ELISA) in 51 patients with AD by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association criteria and compared with 66 age- and gender-matched non-demented controls. Patients with AD were stratified into levels of dementia severity by the Clinical Dementia Rating scale. Serum VEGF levels were stratified into upper (>309 pg/ml), middle (207-309 pg/ml), and lower (<207 pg/ml) tertiles. VEGF (-2,578) (rs 699,947) and VEGF (-634) (rs 2,010,963) polymorphisms were genotyped in patients with AD and controls.


RESULTS
The mean concentration of VEGF in the serum of patients with AD (215.9 pg/ml, SD 101.5) was significantly lower than that of the controls (308.6 pg/ml, SD 223.9, P = 0.004), and decreased serum VEGF levels were associated with AD in a dose-dependent manner, the lower tertile of serum VEGF levels being associated with a fivefold increased risk for AD when compared with the upper tertile. There was no significant correlation between serum VEGF levels and age, sex, APOE alleles, AD dementia severity nor VEGF gene polymorphisms.


CONCLUSIONS
Decrease in serum VEGF levels could contribute to the neurodegenerative process in AD.
Mateo
I
I
Neurology Service, 'Marqués de Valdecilla' University Hospital, University of Cantabria, Santander, Spain.
Llorca
J
J
Infante
J
J
Rodríguez-Rodríguez
E
E
Fernández-Viadero
C
C
Peña
N
N
Berciano
J
J
Combarros
O
O
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D012737:Sex Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics
D053327:Apolipoprotein E4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A