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CSF synaptic protein concentrations are raised in those with atypical Alzheimer's disease but not frontotemporal dementia.

Journal article
Authors Mica T M Clarke
Ann Brinkmalm
Martha S Foiani
Ione O C Woollacott
Carolin Heller
Amanda Heslegrave
Ashvini Keshavan
Nick C Fox
Jonathan M Schott
Jason D Warren
Kaj Blennow
Henrik Zetterberg
Jonathan D Rohrer
Published in Alzheimer's research & therapy
Volume 11
ISSN 1758-9193
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Links dx.doi.org/10.1186/s13195-019-0564-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurochemistry

Abstract

Increased CSF levels of a number of synaptic markers have been reported in Alzheimer's disease (AD), but little is known about their concentrations in frontotemporal dementia (FTD). We investigated this in three synaptic proteins, neurogranin, SNAP-25, and synaptotagmin-1.CSF samples were analysed from 66 patients with a disorder in the FTD spectrum and 19 healthy controls. Patients were stratified by their tau to Aβ42 ratio: those with a ratio of > 1 considered as having likely AD pathology, i.e. an atypical form of AD ('AD biomarker' group [n = 18]), and < 1 as likely FTD pathology ('FTD biomarker' group [n = 48]). A subgroup analysis compared those in the FTD group with likely tau (n = 7) and TDP-43 (n = 18) pathology. Concentrations of neurogranin were measured using two different ELISAs (Ng22 and Ng36), and concentrations of two SNAP-25 fragments (SNAP-25tot and SNAP-25aa40) and synaptotagmin-1 were measured via mass spectrometry.The AD biomarker group had significantly higher concentrations of all synaptic proteins compared to controls except for synaptotagmin-1 where there was only a trend to increased levels-Ng22, AD mean 232.2 (standard deviation 138.9) pg/ml, controls 137.6 (95.9); Ng36, 225.5 (148.8) pg/ml, 130.0 (80.9); SNAP-25tot, 71.4 (27.9) pM, 53.5 (11.7); SNAP-25aa40, 14.0 (6.3), 7.9 (2.3) pM; and synaptotagmin-1, 287.7 (156.0) pM, 238.3 (71.4). All synaptic measures were significantly higher in the atypical AD group than the FTD biomarker group except for Ng36 where there was only a trend to increased levels-Ng22, 114.0 (117.5); Ng36, 171.1 (75.2); SNAP-25tot, 49.2 (16.7); SNAP-25aa40, 8.2 (3.4); and synaptotagmin-1, 197.1 (78.9). No markers were higher in the FTD biomarker group than controls. No significant differences were seen in the subgroup analysis, but there was a trend to increased levels in those with likely tau pathology.No CSF synaptic proteins have been shown to be abnormal in those with likely FTD pathologically. Higher CSF synaptic protein concentrations of neurogranin, SNAP-25, and synaptotagmin-1 appear to be related to AD pathology.

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