TY - JOUR
T1 - Role of CLU, PICALM, and TNK1 Genotypes in Aging With and Without Alzheimer's Disease
AU - Seripa, Davide
AU - Panza, Francesco
AU - Paroni, Giulia
AU - D’Onofrio, Grazia
AU - Bisceglia, Paola
AU - Gravina, Carolina
AU - Urbano, Maria
AU - Lozupone, Madia
AU - Solfrizzi, Vincenzo
AU - Bizzarro, Alessandra
AU - Boccardi, Virginia
AU - Piccininni, Chiara
AU - Daniele, Antonio
AU - Logroscino, Giancarlo
AU - Mecocci, Patrizia
AU - Masullo, Carlo
AU - Greco, Antonio
PY - 2017
Y1 - 2017
N2 - 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 50â65 years (group 1), 66â80 years (group 2), and 80+ years (group 3) in 569 older subjects without cognitive impairment (NoCI) and 520 Alzheimerâs 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.
AB - 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 50â65 years (group 1), 66â80 years (group 2), and 80+ years (group 3) in 569 older subjects without cognitive impairment (NoCI) and 520 Alzheimerâs 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.
KW - Alzheimerâs disease
KW - Biogerontology
KW - Brain aging
KW - Cellular and Molecular Neuroscience
KW - Cognition
KW - Dementia
KW - Genetics
KW - Alzheimerâs disease
KW - Biogerontology
KW - Brain aging
KW - Cellular and Molecular Neuroscience
KW - Cognition
KW - Dementia
KW - Genetics
UR - http://hdl.handle.net/10807/110508
UR - http://www.springer.com/biomed/neuroscience/journal/12035
U2 - 10.1007/s12035-017-0547-x
DO - 10.1007/s12035-017-0547-x
M3 - Article
SN - 0893-7648
SP - 1
EP - 12
JO - Molecular Neurobiology
JF - Molecular Neurobiology
ER -