The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer's disease and is associated with AD-related depression

Transforming growth factor-beta 1 (TGF-beta 1) is a neurotrophic factor that exerts neuroprotective effects against beta-amyloid-induced neurodegeneration. Recently, a specific impairment of the TGF-beta 1 signaling pathway has been demonstrated in Alzheimer's disease (AD) brain. TGF-beta 1 is also involved in the pathogenesis of depressive disorders, which may occur in 30-40% of AD patients. The TGF-beta 1 gene contains single nucleotide polymorphisms (SNPs) at codon +10 (TIC) and +25 (G/C), which are known to influence the level of expression of TGF-beta 1. We investigated TGF-beta 1 +10 (TIC) and +25 (G/C) SNPs and allele frequencies in 131 sporadic AD patients and in 135 healthy age- and sex-matched controls. Genotypes of the TGF-beta 1 SNPs at codon +10 (TIC) and +25 (G/C) did not differ between AD patients and controls, whereas the allele frequencies of codon +10 polymorphism showed a significant difference (P=0.0306). We also found a different distribution of the +10 (C/C) phenotype (continuity-corrected chi(2) test with one degree of freedom=4.460, P=0.0347) between late onset AD (LOAD) patients and controls (P=0.0126), but not between early onset AD (EOAD) patients and controls. In addition, the presence of the C/C genotype increased the risk of LOAD regardless of the status of apolipoprotein E4 (odds ratio [OR]=2.34; 95% CI = 1.19-4.59). Compared to patients bearing the TIT and C/T polymorphisms, LOAD TGF-beta 1 C/C carriers also showed >5-fold risk to develop depressive symptoms independently of a history of depression (OR=5.50; 95% CI=1.33-22.69). An association was also found between the TGF-beta 1 C/C genotype and the severity of depressive symptoms (HAM-D-17 >= 14) (P<0.05). These results suggest that the CC genotype of the TGF-beta 1 gene increases the risk to develop LOAD and is also associated with depressive symptoms in AD. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.