Plasma biomarkers of brain atrophy in Alzheimer's disease.

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 pro...

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Main Authors: Madhav Thambisetty, Andrew Simmons, Abdul Hye, James Campbell, Eric Westman, Yi Zhang, Lars-Olof Wahlund, Anna Kinsey, Mirsada Causevic, Richard Killick, Iwona Kloszewska, Patrizia Mecocci, Hilkka Soininen, Magda Tsolaki, Bruno Vellas, Christian Spenger, Simon Lovestone, AddNeuroMed Consortium
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0028527&type=printable
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author Madhav Thambisetty
Andrew Simmons
Abdul Hye
James Campbell
Eric Westman
Yi Zhang
Lars-Olof Wahlund
Anna Kinsey
Mirsada Causevic
Richard Killick
Iwona Kloszewska
Patrizia Mecocci
Hilkka Soininen
Magda Tsolaki
Bruno Vellas
Christian Spenger
Simon Lovestone
AddNeuroMed Consortium
author_facet Madhav Thambisetty
Andrew Simmons
Abdul Hye
James Campbell
Eric Westman
Yi Zhang
Lars-Olof Wahlund
Anna Kinsey
Mirsada Causevic
Richard Killick
Iwona Kloszewska
Patrizia Mecocci
Hilkka Soininen
Magda Tsolaki
Bruno Vellas
Christian Spenger
Simon Lovestone
AddNeuroMed Consortium
author_sort Madhav Thambisetty
collection DOAJ
description 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.
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spelling doaj-art-3154edc1e20d44daa20385f19cad5c522025-08-20T03:10:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2852710.1371/journal.pone.0028527Plasma biomarkers of brain atrophy in Alzheimer's disease.Madhav ThambisettyAndrew SimmonsAbdul HyeJames CampbellEric WestmanYi ZhangLars-Olof WahlundAnna KinseyMirsada CausevicRichard KillickIwona KloszewskaPatrizia MecocciHilkka SoininenMagda TsolakiBruno VellasChristian SpengerSimon LovestoneAddNeuroMed ConsortiumPeripheral 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0028527&type=printable
spellingShingle Madhav Thambisetty
Andrew Simmons
Abdul Hye
James Campbell
Eric Westman
Yi Zhang
Lars-Olof Wahlund
Anna Kinsey
Mirsada Causevic
Richard Killick
Iwona Kloszewska
Patrizia Mecocci
Hilkka Soininen
Magda Tsolaki
Bruno Vellas
Christian Spenger
Simon Lovestone
AddNeuroMed Consortium
Plasma biomarkers of brain atrophy in Alzheimer's disease.
PLoS ONE
title Plasma biomarkers of brain atrophy in Alzheimer's disease.
title_full Plasma biomarkers of brain atrophy in Alzheimer's disease.
title_fullStr Plasma biomarkers of brain atrophy in Alzheimer's disease.
title_full_unstemmed Plasma biomarkers of brain atrophy in Alzheimer's disease.
title_short Plasma biomarkers of brain atrophy in Alzheimer's disease.
title_sort plasma biomarkers of brain atrophy in alzheimer s disease
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0028527&type=printable
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