title: Proteome-based plasma biomarkers for Alzheimer's disease.
abstract: Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.
authors.affiliation: King's College London, MRC Centre for Neurodegeneration Research London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hye
authors.forename: S
authors.initials: S
authors.lastname: Lynham
authors.forename: M
authors.initials: M
authors.lastname: Thambisetty
authors.forename: M
authors.initials: M
authors.lastname: Causevic
authors.forename: J
authors.initials: J
authors.lastname: Campbell
authors.forename: H L
authors.initials: HL
authors.lastname: Byers
authors.forename: C
authors.initials: C
authors.lastname: Hooper
authors.forename: F
authors.initials: F
authors.lastname: Rijsdijk
authors.forename: S J
authors.initials: SJ
authors.lastname: Tabrizi
authors.forename: S
authors.initials: S
authors.lastname: Banner
authors.forename: C E
authors.initials: CE
authors.lastname: Shaw
authors.forename: C
authors.initials: C
authors.lastname: Foy
authors.forename: M
authors.initials: M
authors.lastname: Poppe
authors.forename: N
authors.initials: N
authors.lastname: Archer
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.forename: J
authors.initials: J
authors.lastname: Powell
authors.forename: R G
authors.initials: RG
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Sham
authors.forename: M
authors.initials: M
authors.lastname: Ward
authors.forename: S
authors.initials: S
authors.lastname: Lovestone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D017242:Complement Factor H / Q000032:analysis; D003937:Diagnosis, Differential; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000175:diagnosis; D020543:Proteome; D040901:Proteomics / Q000379:methods; D012680:Sensitivity and Specificity; D000511:alpha-Macroglobulins / Q000032:analysis
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; C493495:CFH protein, human; D020543:Proteome; D000511:alpha-Macroglobulins; D017242:Complement Factor H