CSF Multianalyte Profile Distinguishes Alzheimer and Parkinson Diseases

The therapeutic imperative for Alzheimer disease (AD) and Parkinson disease (PD) calls for discovery and validation of biomarkers. Increased cerebrospinal fluid (CSF) τ and decreased amyloid (A) β 42 have been validated as biomarkers of AD. In contrast, there is no validated CSF biomarker for PD. We validated our proteomics-discovered multianalyte profile (MAP) in CSF from 95 control subjects, 48 patients with probable AD, and 40 patients with probable PD. An optimal 8-member MAP agreed with expert diagnosis for 90 control subjects (95%), 36 patients with probable AD (75%), and 38 patients with probable PD (95%). This MAP consisted of the following (in decreasing order of contribution): τ, brain-derived neurotrophic factor, interleukin 8, Aβ 42 , β 2 -microglobulin, vitamin D binding protein, apolipoprotein (apo) AII, and apoE. This first large-scale validation of a proteomicdiscovered MAP suggests a panel of 8 CSF proteins that are highly effective at identifying PD and moderately effective at identifying AD. Alzheimer disease (AD) and Parkinson disease (PD) are major public health problems. Key to the effort to obtain new therapeutics will be novel biomarkers to aid in diagnosis, identify subsets of patients, and objectively monitor progression and response to treatment. Several discovery proteomic studies of human cerebrospinal fluid (CSF) have been reported using relatively small numbers of patients with AD compared with control subjects without dementia. 1-6