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CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques

DOI: 10.1186/alzrt71

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We investigated the associations of senile plaques (SP) and neurofibrillary tangles (NFT) with the proposed risk genes and APOE, in the Tampere Autopsy Study (TASTY) series (603 cases), a sample of the general population (0 to 97 yrs), who died out-of-hospital.Age and the APOEε4 allele associated strongly with all phenotypes of SP, as expected. In age and APOEε4 adjusted analyses, compared to the most common homozygous genotype, burnt out SP were more common among carriers of the C-allele of CLU, whereas the T-allele of PICALM and C-allele of CR1 were linked with lower SP coverage. We found no significant associations between any of the genetic variants and NFT.Marginal effects from CLU, CR1 and PICALM suggest that these genes have minimal effects on the development of AD lesions.Alzheimer's disease (AD) is the most common form of dementia in Western society and is, and will continue to be, a burden on health systems in the future as the population ages. Age is the largest risk factor for the disease, with higher incidences in older populations [1,2].Identification of genes related to sporadic AD risk has been slow with study groups isolating only one strongly associated gene: APOE [3,4]. The epsilon 4 allele of apolipoprotein E (APOEε4) provides odds ratios (ORs) of between 3 and 25 [5,6] for disease association. APOEε4 is suspected to have a lower effectiveness at transporting cholesterol and is not as efficient at repairing neuronal damage as APOEε3 [7]. One or even two copies of the allele, however, are not sufficient to cause the disease, as many carriers of two ε4 alleles do not develop AD [5].Studies aiming to detect genes associated with disease risk have used heterogeneous AD cohorts and ascertained few polymorphisms with only a minor impact on disease incidence. One of the problems is to distinguish between pure AD, vascular dementia and other dementia types in clinical cohorts [8-10]. The only consistent and currently accepted method for confirming AD is

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