title: Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer's Disease.
abstract: 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.
authors.affiliation: Kings College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.|NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Martina
authors.initials: M
authors.lastname: Sattlecker
authors.affiliation: Kings College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.|NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Mizanur
authors.initials: M
authors.lastname: Khondoker
authors.affiliation: Kings College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.|NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.affiliation: SomaLogic, Boulder, Colorado, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Williams
authors.affiliation: Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kłoszewska
authors.affiliation: Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: 3rd Department of Neurology, Aristotle University, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: INSERM U 558, University of Toulouse, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Kings College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.|NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Kings College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.|NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Richard Jb
authors.initials: RJ
authors.lastname: Dobson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000523:psychology*; D015415:Biomarkers / Q000097:blood; D003071:Cognition / Q000502:physiology; D060825:Cognitive Dysfunction / Q000097:blood / Q000523:psychology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; cognitive decline; complement cascade; cytokine-cytokine receptor interaction; plasma proteins