Serum peptides as candidate biomarkers for dementia with Lewy bodies.

Objective: For diagnosis of dementia with Lewy bodies (DLB), we tried to find blood biomarkers for the disease.

Methods: Serum peptides were comprehensively detected by mass spectrometry. Peptides of interest were identified by tandem mass spectrometry.

Results: One hundred forty-six peptides were detected in a training set consisting of 30 DLB patients, 30 patients with Alzheimer's disease (AD), and 28 healthy control (HC) subjects. Multivariate analysis for discriminating the DLB group from the non-DLB (AD and HC) group using ion intensity of four peptides (2898, 4052, 4090, and 5002 m/z) showed sensitivity of 93.3% and specificity of 87.9% (DLB/nonDLB-4P model). In a testing set consisting of 20 DLB patients, 30 AD patients, and 14 HC subjects, this model showed sensitivity of 90.0% and specificity of 88.6%. DLB/nonDLB-4P model detected 86.7% and 90.0% of the AD patients as non-DLB in the training and testing sets, respectively, and discriminated all the 15 patients with amnestic mild cognitive impairment as non-DLB. Notably, a combination of two peptides (1737 and 5002 m/z) showed sensitivity of 95.0% and specificity of 93.3% for discriminating the DLB group from the AD group (DLB/nonDLB-2P model) in the testing set. The peptides used in these models included fragments from complement 4b, Wnt-2b, and lipopolysaccharide-binding protein, which were reported to be involved in the pathology of DLB or Parkinson's disease and hippocampal neurogenesis.

Conclusions: Serum peptide profiles would provide useful DLB biomarker candidates, which may be implicated in the pathophysiology of the disease.