Background:
Alzheimer's disease (AD) is the most common type of
dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular
amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain;
amyloid beta 1-42 is a marker of
amyloid plaques, while total and phosphorylated tau are markers of NFT formation. Additional
biomarkers associated with disease pathogenesis are needed, for better prognosis, more specific diagnosis, prediction of disease severity and progression and for improved patient classification in clinical trials. The aim of the present study was to evaluate brain-specific
proteins as potential
biomarkers of progression of AD. Methods: Overall, 30 candidate
proteins were quantified in cerebrospinal fluid (CSF) samples from patients with
mild cognitive impairment (MCI) and mild, moderate and severe AD
dementia (n=101) using mass spectrometry-based selected reaction monitoring assays. ELISA was used for
neuronal pentraxin receptor-1 (NPTXR) confirmation. Results: The best discrimination between MCI and more advanced AD stages (moderate and severe
dementia) was observed for
protein NPTXR (area under the curve, AUC=0.799). A statistically different abundance of this
protein was observed between the two groups, with severe AD patients having progressively lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort that included controls, MCI and AD patients. Conclusions: We conclude that NPTXR
protein in CSF is a novel potential
biomarker of AD progression and could have important utility in assessing treatment success in clinical trials.