Affordable Access

Publisher Website

Plasma Biomarkers of Brain Atrophy in Alzheimer's Disease

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
6
Issue
12
Identifiers
DOI: 10.1371/journal.pone.0028527
Keywords
  • Research Article
  • Biology
  • Biochemistry
  • Proteins
  • Plasma Proteins
  • Immunology
  • Immune System
  • Complement System
  • Medicine
  • Diagnostic Medicine
  • Pathology
  • General Pathology
  • Biomarkers
  • Mental Health
  • Psychiatry
  • Dementia
  • Neurology
  • Alzheimer Disease
  • Cognitive Neurology
Disciplines
  • Biology
  • Medicine

Abstract

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, γ-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.

There are no comments yet on this publication. Be the first to share your thoughts.