Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

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Abstract

Objectives

Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort.

Methods

664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique.

Results

At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years.

Conclusions

Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

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Author and article information

Contributors

: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2012

Publication date (Electronic): 11 June 2012

Volume: 7

Issue: 6

Electronic Location Identifier: e34078

Affiliations

[1 ]Brain and Aging Research Program, University of New South Wales, Sydney, Australia

[2 ]School of Psychiatry, University of New South Wales, Sydney, Australia

[3 ]Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia

[4 ]School of Medical Sciences, University of New South Wales, Sydney, Australia

[5 ]Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia

Nathan Kline Institute and New York University School of Medicine, United States of America

Author notes

* E-mail: p.sachdev@ 123456unsw.edu.au

Conceived and designed the experiments: FS AP PS. Performed the experiments: FS KM. Analyzed the data: FS KM. Contributed reagents/materials/analysis tools: FS JC NK WW BC OL. Wrote the paper: FS AP JC NK BC HB GS PS.

Article

Publisher ID: PONE-D-11-20915

DOI: 10.1371/journal.pone.0034078

PMC ID: 3372509

PubMed ID: 22701550

SO-VID: 24b2c09b-e70a-4854-94de-25dde093add5

Copyright © Song et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 19 October 2011

Date accepted : 21 February 2012

Page count

Pages: 11

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