A TGF-β1 polymorphism association with dementia and neuropathologies: The HAAS

The transforming growth factor-β1 (TGF-β1) is involved in post-ischemic neuronal rescue and in β-amyloid turn-over. We hypothesized that the risk for dementia and related neuropathologies is modified by the TGF-β1 functional genetic variants. The association of the TGF-β1 + 29T → C polymorphism with dementia was examined in a sample of 261 cases and 491 controls from the Honolulu-Asia Aging Study, including 282 subjects with autopsy data. Dementia was assessed in 1991 and 1994 by a multi-step protocol and standardized diagnostic criteria. The analysis was adjusted for demographic and vascular factors. Compared to the TT genotype, the TC and the CC genotypes were associated with a reduced risk for vascular dementia (ORTC = 0.28, 95% confidence interval (CI): 0.1–0.9; ORCC = 0.28, CI: 0.1–0.9), microinfarcts (ORCC = 0.31, CI: 0.13–0.71) and cerebral amyloid angiopathy (ORCC = 0.48, CI: 0.2–0.9). The CC genotype was associated with an increase risk of neocortical plaques (ORCC = 4.34, CI: 1.6–11.8). These preliminary data suggest that the TGF genetic variability may be important in the risk of vascular related dementia.