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-ß (Aß) species, pro-inflammatory markers, anti-Aß autoantibodies, and ApoE allele status, respectively. RESULTS: Plasma Aß1-42 was significantly decreased in MCI and AD compared to age-matched controls, whereas Aß1-40 did not differ, but increases with age in healthy controls. The Aß1-42 to Aß1-40 ratio was stepwise decreased from age-matched controls via MCI to AD, and shows a clear correlation with memory scores. Reduced Aß1-42 and Aß1-42 to Aß1-40 ratio have strongly correlated with carrying ApoE ɛ4 allele. Autoantibodies against pyroglutamate-modified Aß, 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 Aß did not differ. CONCLUSION: Comprehensive sample preparation and assay standardization enable reliable usage of plasma Aß for diagnosis of MCI and AD. Anti-pGlu-Aß autoantibodies correlate with cognition, but not with ApoE, supporting the associated plasma Aß analysis with additional and independent information.