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

Author(s): Paolo Bosco, Raffaele Ferri, Maria Grazia Salluzzo, Sabrina Castellano, Maria Signorelli, Ferdinando Nicoletti, Santo Di Nuovo, Filippo Drago, Filippo Caraci.

Journal Name: Current Genomics

Volume 14 , Issue 2 , 2013

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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 β-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, contains 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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Article Details

VOLUME: 14
ISSUE: 2
Year: 2013
Page: [147 - 156]
Pages: 10
DOI: 10.2174/1389202911314020007
Price: $58

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