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Background: Variants in genes encoding enzymes involved in production, aggregation or degradation of beta-amyloid are potential risk factors for sporadic Alzheimer's disease (AD)., Methods: Meta-analyses on AD association with BACE1 exon 5, BACE1 intron 5, FE65 intron 13, CYP46 intron 2, alpha(1)-antichymotrypsine Ala17Thr, bleomycin hydrolase I443V, lectin-like oxidized low-density lipoprotein receptor (OLR1) 3'-UTR (+1071) and (+1073), and very-low-density lipoprotein receptor (VLDLR) 5'-UTR (CGG-repeat) polymorphisms., Results: In BACE1 exon 5, genotype CC+CT acts as a protective factor in Apolipoprotein E (ApoE) epsilon 4 carriers [odds ratio (OR) = 0.57; 95% confidence interval (CI): 0.38-0.88], and as a risk factor in ApoE epsilon 4 non-carriers (OR = 1.33; 95% CI: 1.00-1.78). OLR1 3'-UTR (+1073) allele C is associated with increased risk (OR = 1.23; 95% CI: 1.01-1.50). VLDLR 5'-UTR genotype 2 is associated with increased risk (OR = 1.70; 95% CI: 1.09-2.63) in the Asian population and is protective (OR = 0.48; 95% CI: 0.26-0.86) in the non-Asian population. Other studied polymorphisms are not associated with AD., Conclusions: The overall impact on AD risk of the genes for which meta-analyses are now available is rather limited. Additional meta-analyses of other different genes encoding for A beta production, aggregation and degradation mediators might help in determining the risk profile for AD.

Objective: As transforming growth factor-beta1 (TGF-beta1) determines important neurotrophic and neuroprotective actions, we postulated serum TGF-beta1 levels could be low in Alzheimer's disease (AD), and TGF-beta1 genetic variation could be associated with AD risk through modulating serum TGF-beta1 levels., Methods: TGF-beta1 (-800) (rs 1800468), (-509) (rs 1800469) and (+869) (rs 1982073) polymorphisms were genotyped in 412 AD patients and 406 controls. We measured serum TGF-beta1 levels (by ELISA) in 63 AD patients and compared them with 77 age- and gender-matched non-demented controls., Results: Serum TGF-beta1 levels were not different in AD patients than in controls. Distribution of the allele and genotype frequencies of TGF-beta1 polymorphisms did not differ between AD patients and controls. There was no significant correlation between serum TGF-beta1 levels and TGF-beta1 polymorphisms., Conclusion: Serum TGF-beta1 concentration is not a potential biomarker for AD, and TGF-beta1 genetic variants (-800, -509, and +869) are not risk factors for AD.