SCRN1: A cerebrospinal fluid biomarker correlating with tau in Alzheimer's disease.

Abstract

Secernin-1 (SCRN1) is a neuronal protein that co-localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease. We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n=25) and controls (n=28), clinically diagnosed Parkinson's disease (PD; n=38), multiple system atrophy (MSA; n=31), PSP (n=20), CBD (n=8), healthy controls (n=37), and neuropathology-confirmed AD (n=47). CSF SCRN1 was significantly increased in AD (P<0.01, fold change=1.4) compared to controls (receiver operating characteristic area under the curve=0.78) but not in CBD, PSP, PD, or MSA. CSF SCRN1 positively correlated with CSF total tau (R=0.78, P=1.1×10-13 ), phosphorylated tau181 (R=0.64, P=3.2×10-8 ), and Braak stage and negatively correlated with Mini-Mental State Examination score. CSF SCRN1 is a candidate biomarker of AD, reflecting tau pathology. We developed a parallel reaction monitoring assay to measure secernin-1 (SCRN1) in cerebrospinal fluid (CSF). CSF SCRN1 was increased in Alzheimer's disease compared to healthy controls. CSF SCRN1 remained unchanged in Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration compared to controls. CSF SCRN1 correlated strongly with CSF phosphorylated tau and total tau. CSF SCRN1 increased across Braak stages and negatively correlated with Mini-Mental State Examination score.