SP and NFT variables included the following categorisations as measured by a neuropathologist: inhibitor SB203580 SP (No, Yes), SP type (No Plaques, Diffuse, Primitive, Classic, Burnt Out), SP type 2 (No Plaques, Non-neuritic SP, Neuritic SP), NFT (No, Yes), where reference groups were those with ‘No SP’ or ‘No NFT’ and those with either brain lesion were considered ‘affected’. Semi-quantitative data for SP utilised the categories ‘no’, ‘sparse’, ‘moderate’ and ‘frequent’ SP. Genotyping The ABI Prism 7900HT Sequence Detection System used 1 ??l DNA with PCR primers (Applied Biosystems, Espoo, Finland) for rs11136000 (CLU), rs1408077 (CR1) and rs3851179 (PICALM). All SNPs were in Hardy-Weinberg equilibrium and genotyping confirmed using SDS version 2.2 (Applied Biosystems). Genotyping for APOE has been previously described [16].

Genotyping for the polymorphisms of CLU, CR1 and PICALM were successful for 94%, 97% and 97% of the TASTY cases, respectively. Statistics Logistic regression analyses, with continuous age and APOE??4 carriership as covariates (where possible), were used with SPSS (version 14.0 for Windows; SPSS Finland Oy, Espoo, Finland) to determine associations between the SNPs and AD-related neuropathological lesions. For all SNPs, the most common homozygous genotype was used as the reference group. As previously mentioned, those unaffected by SP or NFT were considered the reference group for the brain lesion categories. When analysing with the cohort split by age groups, the following categories were used: 0 to 49 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, 80+ years, with the youngest group (0 to 49 years) considered the reference group with respect to age, in analyses.

The cohort was also split by gender, where mentioned. Results Autopsy series characteristics The Tampere Autopsy Series (TASTY) (n = 603) comprises consecutive autopsies on males and females aged 0 to 97 years that lived outside institutions or hospitals (see Table ?Table1).1). Females were on average 10 years older than males, Brefeldin_A but males were more likely to have SP compared to females (odds ratio (OR) 2.15, P < 0.0001, 95% confidence intervals (CI) 1.49 to 3.11). When age was divided into five equal-sized groups, each age group was consistently more likely to have SP compared to the youngest group, with each association also highly statistically significant (see Table ?Table2).

2). This was also true for NFT prevalence (see Table ?Table2),2), with females more likely than males to have NFT (OR 2.18, P < 0.0001, CI 1.49 to 3.18). Table 1 TASTY cohort characteristics Table 2 Senile plaque and neurofibrillary so tangle prevalence in the TASTY cohort by age group APOE, CLU, CR1 and PICALM associations with SP As expected, APOE??4 carriership was significantly associated with increased risk of having SP (OR 2.52, P < 0.0001, CI 1.72 to 3.68); having both non-neuritic (OR 2.42, P = 0.003, CI 1.36 to 4.