Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 3 (2), 12

CLU, CR1 and PICALM Genes Associate With Alzheimer's-related Senile Plaques

Affiliations

CLU, CR1 and PICALM Genes Associate With Alzheimer's-related Senile Plaques

Eloise H Kok et al. Alzheimers Res Ther.

Abstract

Introduction: APOE is the strongest risk gene for sporadic Alzheimer's disease (AD) so far. Recent genome wide association studies found links for sporadic AD with CLU and CR1 involved in Aβ clearance, and PICALM affecting intracellular trafficking.

Methods: 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.

Results: 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.

Conclusions: Marginal effects from CLU, CR1 and PICALM suggest that these genes have minimal effects on the development of AD lesions.

Figures

Figure 1
Figure 1
Senile plaque prevalence by age and genotype (APOE, CLU, CR1 and PICALM). CI = confidence interval; OR = odds ratio.
Figure 2
Figure 2
Boxplots of cortical SP coverage (%) according to Aβ staining and genotype (APOE, CLU, CR1 and PICALM).

Similar articles

Cited by 11 PubMed Central articles

See all "Cited by" articles

References

    1. Polvikoski T, Sulkava R, Rastas S, Sutela A, Niinistö L, Notkola I, Verkkoniemi A, Viramo P, Juva K, Haltia M. Incidence of dementia in very elderly individuals: a clinical, neuropathological and molecular genetic study. Neuroepidemiology. 2006;26:76–82. doi: 10.1159/000090252. - DOI - PubMed
    1. Harvey DJ, Beckett LA, Mungas DM. Multivariate modeling of two associated cognitive outcomes in a longitudinal study. J Alzheimers Dis. 2003;5:357–365. - PubMed
    1. Corder E, Saunders A, Strittmatter W, Schmechel D, Gaskell P, Small G, Roses A, Haines J, Pericak-Vance M. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261:921–923. doi: 10.1126/science.8346443. - DOI - PubMed
    1. van Duijn C, Wehnert A, Van Broeckhoven C, Havekes LM, de Knijff P, Cruts M, Hofman A. Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease. Nat Genet. 1994;7:74–78. doi: 10.1038/ng0594-74. - DOI - PubMed
    1. Farrer L, Cupples L, Haines J, Hyman B, Kukull W, Mayeux R, Myers R, Pericak-Vance M, Risch N, van Duijn C. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA. 1997;278:1349–1356. doi: 10.1001/jama.278.16.1349. - DOI - PubMed
Feedback