Format

Send to

Choose Destination
See comment in PubMed Commons below
Arch Gen Psychiatry. 2010 Jul;67(7):739-48. doi: 10.1001/archgenpsychiatry.2010.78.

Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.

Author information

1
King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, England.

Abstract

CONTEXT:

Blood-based analytes may be indicators of pathological processes in Alzheimer disease (AD).

OBJECTIVE:

To identify plasma proteins associated with AD pathology using a combined proteomic and neuroimaging approach.

DESIGN:

Discovery-phase proteomics to identify plasma proteins associated with correlates of AD pathology. Confirmation and validation using immunodetection in a replication set and an animal model.

SETTING:

A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging.

PARTICIPANTS:

Patients with AD, subjects with mild cognitive impairment, and healthy controls with standardized clinical assessments and structural neuroimaging.

MAIN OUTCOME MEASURES:

Association of plasma proteins with brain atrophy, disease severity, and rate of clinical progression. Extension studies in humans and transgenic mice tested the association between plasma proteins and brain amyloid.

RESULTS:

Clusterin/apolipoprotein J was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. Subjects with AD had increased clusterin messenger RNA in blood, but there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression. APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques.

CONCLUSIONS:

These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.

PMID:
20603455
PMCID:
PMC3111021
DOI:
10.1001/archgenpsychiatry.2010.78
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Support Center