Genetics of clusterin isoform expression and Alzheimer's disease risk.

The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon...

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Autores principales:	I-Fang Ling, Jiraganya Bhongsatiern, James F Simpson, David W Fardo, Steven Estus
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99ee7dac0e6d4d618827f496ed6cc3a5
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spelling	oai:doaj.org-article:99ee7dac0e6d4d618827f496ed6cc3a52021-11-18T07:22:49ZGenetics of clusterin isoform expression and Alzheimer's disease risk.1932-620310.1371/journal.pone.0033923https://doaj.org/article/99ee7dac0e6d4d618827f496ed6cc3a52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22506010/?tool=EBIhttps://doaj.org/toc/1932-6203The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon 1 and proximal promoters. The expression of both CLU1 and CLU2 was increased in individuals with significant AD neuropathology. However, only CLU1 was associated with the rs11136000 genotype, with the minor "protective" rs11136000T allele being associated with increased CLU1 expression. Since CLU1 and CLU2 are predicted to encode intracellular and secreted proteins, respectively, we compared their expression; for both CLU1 and CLU2 transfected cells, clusterin is present in the secretory pathway, accumulates in the extracellular media, and is similar in size to clusterin in human brain. Overall, we interpret these results as indicating that the AD-protective minor rs11136000T allele is associated with increased CLU1 expression. Since CLU1 and CLU2 appear to produce similar proteins and are increased in AD, the AD-protection afforded by the rs11136000T allele may reflect increased soluble clusterin throughout life.I-Fang LingJiraganya BhongsatiernJames F SimpsonDavid W FardoSteven EstusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e33923 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q I-Fang Ling Jiraganya Bhongsatiern James F Simpson David W Fardo Steven Estus Genetics of clusterin isoform expression and Alzheimer's disease risk.
description	The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon 1 and proximal promoters. The expression of both CLU1 and CLU2 was increased in individuals with significant AD neuropathology. However, only CLU1 was associated with the rs11136000 genotype, with the minor "protective" rs11136000T allele being associated with increased CLU1 expression. Since CLU1 and CLU2 are predicted to encode intracellular and secreted proteins, respectively, we compared their expression; for both CLU1 and CLU2 transfected cells, clusterin is present in the secretory pathway, accumulates in the extracellular media, and is similar in size to clusterin in human brain. Overall, we interpret these results as indicating that the AD-protective minor rs11136000T allele is associated with increased CLU1 expression. Since CLU1 and CLU2 appear to produce similar proteins and are increased in AD, the AD-protection afforded by the rs11136000T allele may reflect increased soluble clusterin throughout life.
format	article
author	I-Fang Ling Jiraganya Bhongsatiern James F Simpson David W Fardo Steven Estus
author_facet	I-Fang Ling Jiraganya Bhongsatiern James F Simpson David W Fardo Steven Estus
author_sort	I-Fang Ling
title	Genetics of clusterin isoform expression and Alzheimer's disease risk.
title_short	Genetics of clusterin isoform expression and Alzheimer's disease risk.
title_full	Genetics of clusterin isoform expression and Alzheimer's disease risk.
title_fullStr	Genetics of clusterin isoform expression and Alzheimer's disease risk.
title_full_unstemmed	Genetics of clusterin isoform expression and Alzheimer's disease risk.
title_sort	genetics of clusterin isoform expression and alzheimer's disease risk.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/99ee7dac0e6d4d618827f496ed6cc3a5
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Genetics of clusterin isoform expression and Alzheimer's disease risk.

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