title: Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer's disease.
abstract: The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose metabolism. Fewer changes were observed at the asymptomatic than symptomatic stage with seven and 16 proteins altered significantly in aMC and sMC, respectively. This included complement components C3, C5, C6, apolipoproteins A-I, A-IV, C-I and M, histidine-rich glycoprotein, heparin cofactor II and attractin, which are involved in inflammation, lipid metabolism and vascular health. Proteins involved in lipid metabolism differed only at the symptomatic stage, whereas changes in inflammation and vascular health were evident at asymptomatic and symptomatic stages. Due to increasing evidence supporting the usefulness of ADAD as a model for LOAD, these proteins warrant further investigation into their potential association with early stages of LOAD.
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Muenchhoff
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.|Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, New South Wales, Australia.|School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: Centre of Excellence for Alzheimer's disease Research &Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia.
authors.forename: Veer B
authors.initials: VB
authors.lastname: Gupta
authors.affiliation: Centre of Excellence for Alzheimer's disease Research &Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia.|School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Pratishtha
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Raftery
authors.affiliation: University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, USA.|Knight Alzheimer's Disease Research Center at Washington University School of Medicine, St. Louis, USA.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, USA.|Knight Alzheimer's Disease Research Center at Washington University School of Medicine, St. Louis, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Bateman
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, USA.|Knight Alzheimer's Disease Research Center at Washington University School of Medicine, St. Louis, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: Centre of Excellence for Alzheimer's disease Research &Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia.|School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.|Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, New South Wales, Australia.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053764:Presenilin-1 / Q000097:blood / Q000235:genetics; D020543:Proteome / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; C508853:PSEN1 protein, human; D053764:Presenilin-1; D020543:Proteome