Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

Alzheimers Dement. 2020 Feb;16(2):262-272. doi: 10.1016/j.jalz.2019.09.001. Epub 2020 Jan 6.

Abstract

Introduction: Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD).

Methods: Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We measured cerebrospinal fluid neurofilament light (NF-L), neurogranin (Ng), 14-3-3, and YKL-40 proteins.

Results: Biomarkers showed differences in HC subjects versus AD, FTD, and CJD. Disease groups differed between them except AD versus FTD for YKL-40. Only NF-L differed between all stages within the AD continuum. AD and FTD symptomatic mutation carriers presented differences with respect to HC subjects. Applying the AT(N) system, 96% subjects were positive for neurodegeneration if 14-3-3 was used, 94% if NF-L was used, 62% if Ng was used, and 53% if YKL-40 was used.

Discussion: Biomarkers of synapse and neurodegeneration differentiate HC subjects from neurodegenerative dementias and between AD, FTD, and CJD. NF-L and 14-3-3 performed similar to total tau when AT(N) system was applied.

Keywords: 14-3-3; AT(N) system; Alzheimer's disease; Biomarker; Cerebrospinal fluid; Creutzfeldt-Jakob disease; Frontotemporal dementia; MCI due to AD; Mutation carriers; Neu rofilament light; Neurogranin; Preclinical AD; YKL-40.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Axons / pathology*
  • Biomarkers / cerebrospinal fluid*
  • Case-Control Studies
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid*
  • Female
  • Frontotemporal Dementia / cerebrospinal fluid*
  • Humans
  • Inflammation*
  • Male
  • Middle Aged
  • Mutation
  • Neurofilament Proteins / cerebrospinal fluid
  • Neurogranin / cerebrospinal fluid

Substances

  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Neurofilament Proteins
  • neurofilament protein L
  • Neurogranin