Novel CSF biomarkers for frontotemporal lobar degenerations

Neurology. 2010 Dec 7;75(23):2079-86. doi: 10.1212/WNL.0b013e318200d78d. Epub 2010 Nov 3.

Abstract

Objective: To identify antemortem CSF diagnostic biomarkers that can potentially distinguish between the 2 main causes of frontotemporal lobar degeneration (FTLD), i.e., FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with tau pathology (FTLD-tau).

Methods: CSF samples were collected antemortem from 23 patients with FTLD with known pathology to form a autopsy cohort as part of a comparative biomarker study that additionally included 33 living cognitively normal subjects and 66 patients with autopsy-confirmed Alzheimer disease (AD). CSF samples were also collected from 80 living patients clinically diagnosed with frontotemporal dementia (FTD). Levels of 151 novel analytes were measured via a targeted multiplex panel enriched in neuropeptides, cytokines, and growth factors, along with levels of CSF biomarkers for AD.

Results: CSF levels of multiple analytes differed between FTLD-TDP and FTLD-tau, including Fas, neuropeptides (agouti-related peptide and adrenocorticotropic hormone), and chemokines (IL-23, IL-17). Classification by random forest analysis achieved high sensitivity for FTLD-TDP (86%) with modest specificity (78%) in the autopsy cohort. When the classification algorithm was applied to a living FTD cohort, semantic dementia was the phenotype with the highest predicted proportion of FTLD-TDP. When living patients with behavioral variant FTD were examined in detail, those predicted to have FTLD-TDP demonstrated neuropsychological differences vs those predicted to have FTLD-tau in a pattern consistent with previously reported trends in autopsy-confirmed cases.

Conclusions: Clinical cases with FTLD-TDP and FTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenocorticotropic Hormone / cerebrospinal fluid
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid*
  • Cohort Studies
  • DNA-Binding Proteins / metabolism*
  • Female
  • Frontotemporal Lobar Degeneration / cerebrospinal fluid*
  • Frontotemporal Lobar Degeneration / complications
  • Humans
  • Interleukin-17 / cerebrospinal fluid
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests
  • Statistics, Nonparametric
  • Tauopathies / cerebrospinal fluid*
  • Tauopathies / complications

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Interleukin-17
  • Adrenocorticotropic Hormone