Brain-related proteins as potential CSF biomarkers of Alzheimer's disease: A targeted mass spectrometry approach

作者：Begcevic Ilijana; Brinc Davor; Brown Marshall; Martinez Morillo Eduardo; Goldhardt Oliver; Grimmer Timo; Magdolen Viktor; Batruch Ihor; Diamandis Eleftherios P^*

来源：Journal of Proteomics, 2018, 182: 12-20.

DOI：10.1016/j.jprot.2018.04.027

• Alzheimer's disease
• Cerebrospinal fluid
• Biomarkers
• Selected reaction monitoring
• Mass spectrometry

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline. The main disease hallmarks include amyloid beta aggregates and neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF); the core biomarkers amyloid beta 1-42, total and phosphorylated tau protein levels are changed, relative to cognitively normal elderly. Still, there is a need for additional biomarkers which could identify disease more accurately and at an earlier stage, predict severity and be used in research settings. Here we evaluated 30 brain-related proteins as candidate biomarkers of AD. Proteins were quantified in CSF samples from cognitively healthy individuals (n = 23) and patients with mild cognitive impairment (MCI) due to AD (n = 20) or dementia due to AD (n = 10) using selected reaction monitoring mass spectrometry assays. APLP1 protein was increased in MCI relative to control (p < 0.001). The best discrimination between MCI vs. controls was observed with a model combining APLP1 and SPP1 proteins (area under the curve, AUC = 0.84). The strongest associations between protein abundance and disease severity were found for APLP1, CNTN2 and SPP1 proteins, which had a significant correlation with MMSE and CDR tests (p < 0.05). This study identifies new proteins with biomarker potential at various stages of AD severity.

• 出版日期2018-6-30