title: Characterizing Aging, Mild Cognitive Impairment, and Dementia with Blood-Based Biomarkers and Neuropsychology.
abstract: BACKGROUND
  Current treatment in Alzheimer's disease (AD) is initiated at a stage where the brain already has irreversible structural deteriorations. Therefore, the concept of treatment prior to obvious cognitive deficits has become widely accepted, and simple biochemical tests to discriminate normal aging from prodromal or demented stages are now common practice.
  
  
  OBJECTIVE
  The objective of the study was the differentiation of controls, mild cognitive impairment (MCI) and AD patients by novel blood-based assays in combination with neuropsychological tests.
  
  
  METHODS
  In a cross-sectional study, 143 subjects aged 18 to 85 years were recruited. All participants were classified by a comprehensive neuropsychological assessment. Blood samples were analyzed for several amyloid-β (Aβ) species, pro-inflammatory markers, anti-Aβ autoantibodies, and ApoE allele status, respectively.
  
  
  RESULTS
  Plasma Aβ1-42 was significantly decreased in MCI and AD compared to age-matched controls, whereas Aβ1-40 did not differ, but increases with age in healthy controls. The Aβ1-42 to Aβ1-40 ratio was stepwise decreased from age-matched controls via MCI to AD, and shows a clear correlation with memory scores. Reduced Aβ1-42 and Aβ1-42 to Aβ1-40 ratio have strongly correlated with carrying ApoE ɛ4 allele. Autoantibodies against pyroglutamate-modified Aβ, but only a certain subclass, were significantly decreased in AD compared to MCI and age-matched controls, whereas autoantibodies against the unmodified N-terminus of Aβ did not differ.
  
  
  CONCLUSIONS
  Comprehensive sample preparation and assay standardization enable reliable usage of plasma Aβ for diagnosis of MCI and AD. Anti-pGlu-Aβ autoantibodies correlate with cognition, but not with ApoE, supporting the associated plasma Aβ analysis with additional and independent information.
authors.affiliation: Probiodrug AG, Halle (Saale), Germany.|Current address: Fraunhofer Institute of Cell Therapy and Immunology, Department of Drug Design and Target Validation, Halle (Saale), Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kleinschmidt
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Department of Psychology, Halle (Saale), Germany.
authors.forename: Robby
authors.initials: R
authors.lastname: Schoenfeld
authors.affiliation: Probiodrug AG, Halle (Saale), Germany.|Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Wuerzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Göttlich
authors.affiliation: Clinic for Neurology, Otto-von-Guericke University Magdeburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bittner
authors.affiliation: Galmed GmbH, Halle (Saale), Germany.
authors.forename: Jürgen Erich
authors.initials: JE
authors.lastname: Metzner
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Department of Psychology, Halle (Saale), Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Leplow
authors.affiliation: Probiodrug AG, Halle (Saale), Germany.|Current address: Fraunhofer Institute of Cell Therapy and Immunology, Department of Drug Design and Target Validation, Halle (Saale), Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000097:blood; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000097:blood; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D003704:Dementia / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000150:complications; D008875:Middle Aged; D009483:Neuropsychological Tests; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D016207:Cytokines
keywords: Aging; Alzheimer’s disease; ApoE; amyloid-β; autoantibodies; blood; mild cognitive impairment; neuropsychology