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NOVEL CSF BIOMARKERS FOR SYNAPTIC AND LYSOSOMAL FUNCTION IN NEURODEGENERATIVE DISEASES
Abstract
Abstract Body
INTRODUCTION: Synaptic and lysosomal dysfunction are hallmark pathological changes in most neurodegenerative diseases. Thus, identification and validation of biomarkers reflecting synaptic and lysosomal dysfunction to be employed as diagnostic and prognostic biomarkers are greatly needed.
METHOD: Solid-phase extraction and parallel reaction monitoring mass spectrometry methods were used to quantify 17 synaptic proteins and 18 lysosomal proteins in CSF, in cross-sectional studies including Alzheimer's disease (AD) patients, patients with different forms of frontotemporal dementia (FTD), Parkinson's disease (PD) and cognitively normal controls.
RESULTS: Increased concentrations of beta-synuclein, gamma-synuclein, neurogranin, PEBP-1, and 14-3-3 proteins were observed in AD patients compared with controls, while neuronal pentraxin-2 and neuronal pentraxin receptor were decreased. In FTD, multiple markers were abnormal in symptomatic MAPT mutations (beta-synuclein, gamma-synuclein, neurogranin, Rab GDP dissociation factor, 14-3-3 eta, syntaxin 1B, syntaxin 7, PBP1 plus NPTX1 and 2), whilst only neuronal pentraxins were affected in symptomatic C9orf72 and GRN mutation carriers. PD patients showed generally low levels of synaptic and lysosomal proteins in their CSF.
DISCUSSION: We have established methods to quantify synaptic and lysosomal proteins in CSF. The results suggest distinct biomarker patterns across neurodegenerative dementias, which correlate with clinical onset and disease progression. Future studies are now needed to examine how the biomarkers change with time and how they respond to treatment with disease-modifying drug candidates.