TY - JOUR
T1 - Association studies between common variants in prolyl isomerase Pin1 and the risk for late-onset Alzheimer's disease
AU - Nowotny, Petra
AU - Bertelsen, Sarah
AU - Hinrichs, Anthony L.
AU - Kauwe, John S.K.
AU - Mayo, Kevin
AU - Jacquart, Sarah
AU - Morris, John C.
AU - Goate, Alison
N1 - Funding Information:
We are grateful to the subjects for their participation in this study. Funding for this work was provided by grants from the National Institute of Health: P50 AG05681 (to J.C.M.), RO1 AG16208 (to A.G.) and PO1 AG03991 (to J.C.M.). J.S.K.K. is a Ford Foundation Fellow. P.N. is supported by a grant form the Missouri Alzheimer's Association.
PY - 2007/5/23
Y1 - 2007/5/23
N2 - Alzheimer's disease (AD) pathology is associated with two proteins, the microtubule-binding protein tau and the β-amyloid-precursor protein (APP). When tau becomes hyperphosphorylated, it forms neuritic aggregates, called neurofibrillary tangles. APP is cleaved by several enzymes to generate Aβ peptides, which are - depending on their length - more or less amyloidogenic and form senile plaques. Pin1, a peptidyl-propyl cis/trans-isomerase, seems to be involved in both pathologies. Pin1 may facilitate dephosphorylation of tau by PP2A phosphatase, while cellular overexpression of Pin1 causes a reduction in the amyloidogenic processing of APP, making this enzyme an interesting target for pharmaceutical intervention. The gene encoding Pin1 maps to 19p13.2, a region previously linked to late-onset Alzheimer's disease (LOAD). Therefore, Pin1 is an excellent positional and functional candidate for LOAD. In this study, we investigated whether common single nucleotide polymorphisms (SNPs) in Pin1 can influence the risk for developing late-onset Alzheimer's disease. No association was observed with any of six polymorphisms or their resulting haplotypes. A meta-analysis of two promoter SNPs, which combined the data from this study with two previous ones, did not show any association either suggesting that common SNPs in Pin1 do not increase the risk for LOAD.
AB - Alzheimer's disease (AD) pathology is associated with two proteins, the microtubule-binding protein tau and the β-amyloid-precursor protein (APP). When tau becomes hyperphosphorylated, it forms neuritic aggregates, called neurofibrillary tangles. APP is cleaved by several enzymes to generate Aβ peptides, which are - depending on their length - more or less amyloidogenic and form senile plaques. Pin1, a peptidyl-propyl cis/trans-isomerase, seems to be involved in both pathologies. Pin1 may facilitate dephosphorylation of tau by PP2A phosphatase, while cellular overexpression of Pin1 causes a reduction in the amyloidogenic processing of APP, making this enzyme an interesting target for pharmaceutical intervention. The gene encoding Pin1 maps to 19p13.2, a region previously linked to late-onset Alzheimer's disease (LOAD). Therefore, Pin1 is an excellent positional and functional candidate for LOAD. In this study, we investigated whether common single nucleotide polymorphisms (SNPs) in Pin1 can influence the risk for developing late-onset Alzheimer's disease. No association was observed with any of six polymorphisms or their resulting haplotypes. A meta-analysis of two promoter SNPs, which combined the data from this study with two previous ones, did not show any association either suggesting that common SNPs in Pin1 do not increase the risk for LOAD.
KW - Genotyping
KW - Late-onset Alzheimer's disease
KW - Pin1
UR - http://www.scopus.com/inward/record.url?scp=34247867974&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2007.03.071
DO - 10.1016/j.neulet.2007.03.071
M3 - Article
C2 - 17482359
AN - SCOPUS:34247867974
SN - 0304-3940
VL - 419
SP - 15
EP - 17
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -