Plasma Biomarkers of Brain Atrophy in Alzheimer's Disease

被引：95

作者：

Thambisetty, Madhav ^{[1
]}

Simmons, Andrew ^{[2
]}

Hye, Abdul ^{[2
]}

Campbell, James ^{[3
]}

Westman, Eric ^{[2
]}

Zhang, Yi ^{[4
]}

Wahlund, Lars-Olof ^{[5
]}

Kinsey, Anna ^{[2
]}

Causevic, Mirsada ^{[2
]}

Killick, Richard ^{[2
]}

Kloszewska, Iwona ^{[6
]}

Mecocci, Patrizia ^{[7
]}

Soininen, Hilkka ^{[8
,9
]}

Tsolaki, Magda ^{[10
]}

Vellas, Bruno ^{[11
]}

Spenger, Christian ^{[4
]}

Lovestone, Simon ^{[1
]}

机构：

[1] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA

[2] Kings Coll London, Inst Psychiat, London WC2R 2LS, England

[3] Proteome Sci Plc, Cobham, England

[4] Karolinska Inst, Div Radiol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden

[5] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Sect Clin Geriatr, Stockholm, Sweden

[6] Med Univ Lodz, Dept Old Age Psychiat & Psychot Disorders, Lodz, Poland

[7] Univ Perugia, Dept Clin & Expt Med, Sect Gerontol & Geriatr, I-06100 Perugia, Italy

[8] Kuopio Univ Hosp, SF-70210 Kuopio, Finland

[9] Univ Eastern Finland, Dept Neurol, Kuopio, Finland

[10] Aristotle Univ Thessaloniki, Dept Neurol, GR-54006 Thessaloniki, Greece

[11] Hop Toulouse, Dept Internal & Geriatr Med, Toulouse, France

来源：

PLOS ONE | 2011年 / 6卷 / 12期

关键词：

CEREBROSPINAL-FLUID BIOMARKERS; CLUSTERIN CONCENTRATION; COMPLEMENT; DEMENTIA; PROTEINS; PROGRESSION; PREDICTION; TRIALS;

D O I：

10.1371/journal.pone.0028527

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Peripheral biomarkers of Alzheimer's disease (AD) reflecting early neuropathological change are critical to the development of treatments for this condition. The most widely used indicator of AD pathology in life at present is neuroimaging evidence of brain atrophy. We therefore performed a proteomic analysis of plasma to derive biomarkers associated with brain atrophy in AD. Using gel based proteomics we previously identified seven plasma proteins that were significantly associated with hippocampal volume in a combined cohort of subjects with AD (N = 27) and MCI (N = 17). In the current report, we validated this finding in a large independent cohort of AD (N = 79), MCI (N = 88) and control (N = 95) subjects using alternative complementary methods-quantitative immunoassays for protein concentrations and estimation of pathology by whole brain volume. We confirmed that plasma concentrations of five proteins, together with age and sex, explained more than 35% of variance in whole brain volume in AD patients. These proteins are complement components C3 and C3a, complement factor-I, gamma-fibrinogen and alpha-1-microglobulin. Our findings suggest that these plasma proteins are strong predictors of in vivo AD pathology. Moreover, these proteins are involved in complement activation and coagulation, providing further evidence for an intrinsic role of these pathways in AD pathogenesis.

引用

页数：7

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