Plasma Biomarkers Associated With the Apolipoprotein E Genotype and Alzheimer Disease

Background: A blood-based test that could be used as a screen for Alzheimer disease (AD) may enable early intervention and better access to treatment. Objective: To apply a multiplex immunoassay panel to identify plasma biomarkers of AD using plasma samples from the Alzheimer's Disease Neuroimaging Initiative cohort. Design: Cohort study. Setting: The Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project. Participants: Plasma samples at baseline and at 1 year were analyzed from 396 (345 at 1 year) patients with mild cognitive impairment, 112 (97 at 1 year) patients with AD, and 58 (54 at 1 year) healthy control subjects. Main Outcome Measures: Multivariate and univariate statistical analyses were used to examine differences across diagnostic groups and relative to the apolipoprotein E (ApoE) genotype. Results: Increased levels of eotaxin 3, pancreatic polypeptide, and N-terminal protein B-type brain natriuretic peptide were observed in patients, confirming similar changes reported in cerebrospinal fluid samples of patients with AD and MCI. Increases in tenascin C levels and decreases in IgM and ApoE levels were also observed. All participants with Apo epsilon 3/epsilon 4 or epsilon 4/epsilon 4 alleles showed a distinct biochemical profile characterized by low C-reactive protein and ApoE levels and by high cortisol, interleukin 13, apolipoprotein B, and gamma interferon levels. The use of plasma biomarkers improved specificity in differentiating patients with AD from controls, and ApoE plasma levels were lowest in patients whose mild cognitive impairment had progressed to dementia. Conclusions: Plasma biomarker results confirm cerebrospinal fluid studies reporting increased levels of pancreatic polypeptide and N-terminal protein B-type brain natriuretic peptide in patients with AD and mild cognitive impairment. Incorporation of plasma biomarkers yielded high sensitivity with improved specificity, supporting their usefulness as a screening tool. The ApoE genotype was associated with a unique biochemical profile irrespective of diagnosis, highlighting the importance of genotype on blood protein profiles.