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

Filippo Caraci, Paolo Bosco, Maria Signorelli, Rosario S. Spada, Filomena I. Cosentino, Giuseppe Toscano, Cinzia Bonforte, Stefano Muratore, Giuseppina Prestianni, Simonetta Panerai, Maria Concetta Giambirtone, Eleonora Gulotta, Carmelo Romano, Maria Grazia Salluzzo, Ferdinando Nicoletti, Agata Copani, Filippo Drago, Eugenio Aguglia, Raffaele Ferri

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish
Pages (from-to)281-289
Number of pages9
JournalEuropean Neuropsychopharmacology
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 2012

Keywords

  • Alzheimer's disease;
  • Depression;
  • Genetic polymorphism;
  • Risk factor
  • Transforming-Growth-Factor-β1;

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

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