Title:Role of the Transforming-Growth-Factor-β1 Gene in Late-Onset Alzheimer’s Disease: Implications for the Treatment
VOLUME: 14 ISSUE: 2
Author(s):Paolo Bosco, Raffaele Ferri, Maria Grazia Salluzzo, Sabrina Castellano, Maria Signorelli, Ferdinando Nicoletti, Santo Di Nuovo, Filippo Drago and Filippo Caraci
Affiliation:IRCCS Associazione Oasi Maria S.S. Institute for Research on Mental Retardation and Brain Aging, 94018 Troina, Enna, Italy.
Keywords:Alzheimer’s disease, Depression, Drugs, Genetic polymorphism, Risk factor, Transforming-growth-factor-β1
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.
