Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study

Background. Senile systemic amyloidosis (SSA) is characterized by deposition of wild-type transthyretin (TTR)-based amyloid in parenchymal organs in elderly individuals. Previously, no population-based studies have been performed on SSA. Methods. Here we have studied the prevalence and risk factors for SSA in a Finnish autopsied population aged 85 or over, as part of the population-based Vantaa 85+ Autopsy Study (n=256). The diagnosis of SSA was based on histological examination of myocardial samples stained with Congo red and anti-TTR immunohistochemistry. The genotype frequencies of 20 polymorphisms in 9 genes in subjects with and without SSA were compared. Results. The prevalence of SSA was 25%. SSA was associated with age, myocardial infarctions, the G/G (Val/Val) genotype of the exon 24 polymorphism in the alpha2-macroglobulin (alpha 2M), and the H2 haplotype of the tau gene (F-values 0.002, 0.004, 0.042, and 0.016). Conclusion. This population-based study shows that SSA is very common in old individuals, affecting one-quarter of people aged over 85 years. Myocardial infarctions and variation in the genes for alpha 2M and tau may be associated with SSA.