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

Eur Neuropsychopharmacol. 2012 Apr;22(4):281-9. doi: 10.1016/j.euroneuro.2011.08.006. Epub 2011 Sep 15.


Transforming growth factor-β1 (TGF-β1) is a neurotrophic factor that exerts neuroprotective effects against β-amyloid-induced neurodegeneration. Recently, a specific impairment of the TGF-β1 signaling pathway has been demonstrated in Alzheimer's disease (AD) brain. TGF-β1 is also involved in the pathogenesis of depressive disorders, which may occur in 30-40% of AD patients. The TGF-β1 gene contains single nucleotide polymorphisms (SNPs) at codon +10 (T/C) and +25 (G/C), which are known to influence the level of expression of TGF-β1. We investigated TGF-β1 +10 (T/C) 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-β1 SNPs at codon +10 (T/C) 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 χ(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 T/T and C/T polymorphisms, LOAD TGF-β1 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-β1 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-β1 gene increases the risk to develop LOAD and is also associated with depressive symptoms in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Apolipoprotein E4 / blood
  • Case-Control Studies
  • Depression / complications
  • Depression / genetics*
  • Depression / psychology
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Predisposition to Disease / psychology
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Transforming Growth Factor beta1 / genetics*


  • Apolipoprotein E4
  • Transforming Growth Factor beta1