Role of CLU, PICALM, and TNK1 Genotypes in Aging With and Without Alzheimer’s Disease

Davide Seripa, Francesco Panza, Giulia Paroni, Grazia D’Onofrio, Paola Bisceglia, Carolina Gravina, Maria Urbano, Madia Lozupone, Vincenzo Solfrizzi, Alessandra Bizzarro, Virginia Boccardi, Chiara Piccininni, Antonio Daniele, Giancarlo Logroscino, Patrizia Mecocci, Carlo Masullo, Antonio Greco

Research output: Contribution to journalArticlepeer-review

Abstract

Healthy and impaired cognitive aging may be associated to different prevalences of single-nucleotide polymorphisms (SNPs). In a multicenter case-control association study, we studied the SNPs rs11136000 (clusterin, CLU), rs541458 (phosphatidylinositol binding clatrin assembly protein, PICALM), and rs1554948 (transcription factor A, and tyrosine kinase, non-receptor, 1, TNK1) according to the three age groups 50–65 years (group 1), 66–80 years (group 2), and 80+ years (group 3) in 569 older subjects without cognitive impairment (NoCI) and 520 Alzheimer’s disease (AD) patients. In NoCI subjects, a regression analysis suggested a relationship between age and TNK1 genotypes, with the TNK1-A/A genotype frequency that increased with higher age, and resulting in a different distribution of the TNK1-A allele. In AD patients, a regression analysis suggested a relationship between age and PICALM genotypes and TNK1 genotypes, with the PICALM-T/C and TNK1-A/A genotype frequencies that decreased with increasing age. A resulting difference in the distribution of PICALM-C allele and TNK1-A allele was also observed. The TNK1-A allele was overrepresented in NoCI subjects than in AD patients in age groups 2 and 3. These results confirmed after adjustment for apolipoprotein E polymorphism, which suggested a different role of PICALM and TNK1 in healthy and impaired cognitive aging. More studies, however, are needed to confirm the observed associations.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalMolecular Neurobiology
DOIs
Publication statusAccepted/In press - Jun 19 2017

Keywords

  • Alzheimer’s disease
  • Biogerontology
  • Brain aging
  • Cognition
  • Dementia
  • Genetics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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