clusterin濃度：アルツハイマー病重症度・病理・発症と関連

アルツハイマー型認知症の血中検査ができれば、診断に助かるだろう。

Thambisetty M et al. "Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease" Arch Gen Psychiatry 2010; 67(7): 739-748.

Clusterin/apolipoprotein J は、entorhinal cortex萎縮、baseline disease severity、ADの臨床的急激な進行と相関
clusterin濃度増加はmedial temporal lobeのfibrillar amyloid-β burdenの増大の予測因子

AD患者は血中の clusterin messenger RNA増加するが、遺伝子・蛋白発現としてのSNPｓの影響はない。
APP/PS1 transgenic マウスでは、年齢依存的な、脳のclusterinの増加、プラーク内のアミロイド、clusterin濃度の増加が見られた。

clusterinとアルツハイマー型認知症に関する先行する報告

Harold D, Abraham R, Hollingworth P, et al. (September 2009). "Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease". Nat. Genet. 41 (10): 1088–93. doi:10.1038/ng.440. PMID 19734902.

Lambert JC, Heath S, Even G, et al. (September 2009). "Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease". Nat. Genet. 41 (10): 1094–9. doi:10.1038/ng.439. PMID 19734903.

http://www.vincibiochem.it/PDFfiles/Clusterin-Apolipoprotein%20J.pdf

Clusterin [CLU [1]; Apo-J [2]; TRPM-2 [3]; SGP2 [4]; NA1/NA2 [5]; CLI; SP-40,40 [6]] is a chaperone-like molecule capable of interacting with various proteins.
It has been first isolated from rat testes fluid and was found to be able to “cluster” red blood cells [1].
Widely expressed in mammalian tissues, clusterin has been implicated in many diverse physiological processes such as lipid transportation, complement inhibition, sperm maturation, tissue remodeling, cell-cell and cell-substrate interactions, membrane recycling and stabilization of stressed proteins in a folding-competent state.
The main product of the clusterin gene is a ~60 kDa pre-secretory form (pre-sCLU), which is targeted to the ER by an initial leader peptide.
As the protein is transported towards the Golgi it becomes glycosylated and cleaved into α and β subunits.
The secreted form of clusterin (sCLU) arise when both subunits become linked by disulfide bridges to form a heterodimeric protein of about 80 kDa.
Secreted clusterin is a major protein of physiological fluids such as plasma, milk, urine, cerebrospinal fluid and semen.
Recently, a smaller isoform of 50-55 kDa has been identified. This nuclear form (nCLU) results from a second transcript and localizes to the nucleus [7].