BACKGROUND: A recent study showed that transforming growth factor-beta1 (TGF-beta1) induces amyloid-beta deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer's disease (AD), and that TGF-beta1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in human AD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 gene has been reported to be associated with the serum TGF-beta1 concentration. We investigated whether the TGF-beta1 polymorphism is associated with the risk of CAA. METHODS: The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E (APOE) genotype was also determined. RESULTS: The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-AD patients (p = 0.011), and APOE non-epsilon4 carriers (p = 0.0099), but not in AD patients or APOE epsilon4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-AD patients (p = 0.0026), and APOE non-epsilon4 carriers (p = 0.0028), but not in AD patients or APOE epsilon4 carriers. The polymorphism was not significantly associated with AD. CONCLUSIONS: Our results suggest that the polymorphism in TGF-beta1 is associated with the severity of CAA, especially in non-AD patients and APOE non-epsilon4 carriers.
BACKGROUND: A recent study showed that transforming growth factor-beta1 (TGF-beta1) induces amyloid-beta deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer's disease (AD), and that TGF-beta1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in humanAD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 gene has been reported to be associated with the serum TGF-beta1 concentration. We investigated whether the TGF-beta1 polymorphism is associated with the risk of CAA. METHODS: The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E (APOE) genotype was also determined. RESULTS: The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-ADpatients (p = 0.011), and APOE non-epsilon4 carriers (p = 0.0099), but not in ADpatients or APOE epsilon4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-ADpatients (p = 0.0026), and APOE non-epsilon4 carriers (p = 0.0028), but not in ADpatients or APOE epsilon4 carriers. The polymorphism was not significantly associated with AD. CONCLUSIONS: Our results suggest that the polymorphism in TGF-beta1 is associated with the severity of CAA, especially in non-ADpatients and APOE non-epsilon4 carriers.
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