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. 2013 Apr;14(2):147-56.
doi: 10.2174/1389202911314020007.

Role of the Transforming-Growth-Factor-β1 Gene in Late-Onset Alzheimer's Disease: Implications for the Treatment

Paolo Bosco  1 , Raffaele Ferri, Maria Grazia Salluzzo, Sabrina Castellano, Maria Signorelli, Ferdinando Nicoletti, Santo Di Nuovo, Filippo Drago, Filippo Caraci
Affiliations

Role of the Transforming-Growth-Factor-β1 Gene in Late-Onset Alzheimer's Disease: Implications for the Treatment

Paolo Bosco et al. Curr Genomics. 2013 Apr.

Abstract

Late-onset Alzheimer's disease (LOAD) is the most common form of dementia in the elderly. LOAD has a complex and largely unknown etiology with strong genetic determinants. Genetics of LOAD is known to involve several genetic risk factors among which the Apolipoprotein E (APOE) gene seems to be the major recognized genetic determinant. Recent efforts have been made to identify other genetic factors involved in the pathophysiology of LOAD such as genes associated with a deficit of neurotrophic factors in the AD brain. Genetic variations of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), and transforming-growth-factor-β1 (TGF-β1) are known to increase the risk to develop LOAD and have also been related to depression susceptibility in LOAD. Transforming-Growth-Factor-β1 (TGF-β1) is a neurotrophic factor that exerts neuroprotective effects against ß-amyloid-induced neurodegeneration. Recent evidence suggests that a specific impairment in the signaling of TGF-β is an early event in the pathogenesis of AD. TGF-β1 protein levels are predominantly under genetic control, and the TGF-β1 gene, located on chromosome 19q13.1-3, con-tains several single nucleotide polymorphisms (SNPs) upstream and in the transcript region, such as the SNP at codon +10 (T/C) and +25 (G/C), which is known to influence the level of expression of TGF-β1. In the present review, we summarize the current literature on genetic risk factors for LOAD, focusing on the role of the TGF-β1 gene, finally discussing the possible implications of these genetic studies for the selection of patients eligible for neuroprotective strategies in AD.

Keywords: Alzheimer’s disease; Depression; Drugs; Genetic polymorphism; Risk factor; Transforming-growth-factor-β1..

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