Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer's Disease

TY - JOUR

T1 - Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer's Disease

AU - Sattlecker, Martina

AU - Khondoker, Mizanur

AU - Proitsi, Petroula

AU - Williams, Stephen

AU - Soininen, Hilkka

AU - K??oszewska, Iwona

AU - Mecocci, Patrizia

AU - Tsolaki, Magda

AU - Vellas, Bruno

AU - Lovestone, Simon

AU - Dobson, Richard Jb

PY - 2015/11/23

Y1 - 2015/11/23

N2 - Biomarkers of Alzheimer’s disease (AD) progression are needed to support the development of urgently needed disease modifying drugs. We employed a SOMAscan assay for quantifying 1,001 proteins in blood samples from 90 AD subjects, 37 stable mild cognitive impaired (MCI) subjects, 39 MCI subjects converting to AD within a year and 69 controls at baseline and one year follow up. We used linear mixed effects models to identify proteins changing significantly over one year with the rate of cognitive decline, which was quantified as the reduction in Mini Mental State Examination (MMSE) scores. Additionally, we investigated proteins changing differently across disease groups and during the conversion from MCI to AD. We found that levels of proteins belonging to the complement cascade increase significantly in fast declining AD patients. Longitudinal changes in the complement cascade might be a surrogate biomarker for disease progression. We also found that members of the cytokine-cytokine receptor interaction pathway change during AD when compared to healthy aging subjects.

AB - Biomarkers of Alzheimer’s disease (AD) progression are needed to support the development of urgently needed disease modifying drugs. We employed a SOMAscan assay for quantifying 1,001 proteins in blood samples from 90 AD subjects, 37 stable mild cognitive impaired (MCI) subjects, 39 MCI subjects converting to AD within a year and 69 controls at baseline and one year follow up. We used linear mixed effects models to identify proteins changing significantly over one year with the rate of cognitive decline, which was quantified as the reduction in Mini Mental State Examination (MMSE) scores. Additionally, we investigated proteins changing differently across disease groups and during the conversion from MCI to AD. We found that levels of proteins belonging to the complement cascade increase significantly in fast declining AD patients. Longitudinal changes in the complement cascade might be a surrogate biomarker for disease progression. We also found that members of the cytokine-cytokine receptor interaction pathway change during AD when compared to healthy aging subjects.

U2 - 10.3233/JAD-140669

DO - 10.3233/JAD-140669

M3 - Article

SN - 1387-2877

VL - 49

SP - 1105

EP - 1114

JO - JOURNAL OF ALZHEIMERS DISEASE

JF - JOURNAL OF ALZHEIMERS DISEASE

IS - 4

ER -