Role of CLU, PICALM, and TNK1 Genotypes in Aging With and Without Alzheimer’s Disease
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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.
KeywordsBiogerontology Brain aging Cognition Dementia Genetics Alzheimer’s disease
This study was completely supported by “Ministero della Salute,” I.R.C.C.S. Research Program, Ricerca Corrente 2015-2017, Linea n. 2 “Malattie complesse e terapie innovative” and by the “5 × 1000” voluntary contribution. We wish to thank Dr. Michele Lauriola for help us for the management of electronic databases.
Davide Seripa, Francesco Panza, and Antonio Greco conceived and designed the study, interpreted the data, wrote the manuscript, and are the guarantors for the study. Giulia Paroni, Grazia D’Onofrio, Madia Lozupone, and Antonio Daniele assisted in literature search, interpretation of data and manuscript preparation. Davide Seripa and Vincenzo Solfrizzi assisted in study design and in the data interpretation, performed the statistical analysis, and had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Paola Bisceglia, Carolina Gravina, Maria Urbano, Alessandra Bizzarro, Virginia Boccardi, and Chiara Piccininni performed genetic analyses in the three study sites and assisted in interpretation of data and manuscript preparation. Giancarlo Logroscino, Patrizia Mecocci, and Carlo Masullo participated to the interpretation of the data and performed the internal review process.
Compliance with Ethical Standards
This was a multicenter case-control association study fulfilling the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The approval of the study for experiments using human subjects was obtained from the local Ethics Committees on human experimentation. Written informed consent for research was obtained from each patient or from relatives/legal caregiver in case of critically disabled demented patients. Statements related to ethics/ethical standards must be presented in the back matter. Thus, the relevant text was copied and captured under "Compliance with....”This query is not clear. Statements related to ethics/ethical standards are presented in the back matter, i.e. after the acknowledgements.
Conflicts of Interest
The authors declare that they have no conflict of interest.
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