+10 T/C polymorphisms in the gene of transforming growth factor-β1 are associated with neurodegeneration and its clinical evolution

Transforming growth factor-β1 (TGF-β1) acts as an immunosuppressant by inhibiting the expression of several pro-inflammatory cytokines. Its gene contains single nucleotide polymorphisms (SNPs) at codon +10 (T → C) and +25 (G → C) that appear to influence the level of expression of TGF-β1. We investigated these SNPs in 198 healthy controls (HC), 193 patients with Alzheimer's disease (AD) and 48 patients with mild cognitive impairment (MCI). Among the latter, after a 4-year follow-up, 21 were diagnosed as AD (MCI → AD) while 18 did not progress (stable MCI). We observed that both the +10 C allele and the CC genotype were over-represented in AD when compared to HC. These variants significantly raised the risk of disease independently of the status of apolipoprotein E4. The CC genotype was also over-expressed in MCI, especially in MCI → AD. These results suggest that TGF-β1 may be one of the early markers involved in the inflammatory mechanisms underlying the pathogenesis of AD.