Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases

Inga Zerr, Matthias Schmitz, André Karch, Anna Villar-Piqué, Eirini Kanata, Ewa Golanska, Daniela Díaz-Lucena, Aikaterini Karsanidou, Peter Hermann, Tobias Knipper, Stefan Goebel, Daniela Varges, Theodoros Sklaviadis, Beata Sikorska, Pawel P. Liberski, Isabel Santana, Isidro Ferrer, Henrik Zetterberg, Kaj Blennow, Olga CaleroMiguel Calero, Anna Ladogana, Raquel Sánchez-Valle, Inês Baldeiras, Franc Llorens

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown. Methods: Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n = 122), mild cognitive impairment (n = 48), Alzheimer's disease (n = 108), dementia with Lewy bodies/Parkinson's disease dementia (n = 53), vascular dementia (n = 46), frontotemporal dementia (n = 41), sporadic Creutzfeldt-Jakob disease (sCJD, n = 132), and genetic prion diseases (n = 182). Results: The highest NFL levels were detected in sCJD, followed by vascular dementia, frontotemporal dementia, dementia with Lewy bodies/Parkinson's disease dementia, Alzheimer's disease, and mild cognitive impairment. In sCJD, NFL levels correlated with cerebrospinal fluid tau and disease duration. NFL levels were able to differentiate sCJD from nonprimarily neurodegenerative neurological and psychiatric diseases (area under the curve = 0.99, 95% confidence interval: 0.99–1) and from the other diagnostic groups showing cognitive impairment/dementia of a non-CJD etiology (area under the curve = 0.90, 95% confidence interval: 0.87–0.92). Compared to nonprimarily neurodegenerative neurological and psychiatric diseases, NFL was also elevated in genetic prion diseases associated with the E200K, V210I, P102L, and D178N prion protein gene mutations. Discussion: Increased NFL levels are a common feature in neurodegenerative dementias.

Original languageEnglish
Pages (from-to)751-763
Number of pages13
JournalAlzheimer's and Dementia
Volume14
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Keywords

  • Alzheimer's disease
  • Cerebrospinal fluid
  • Dementia with Lewy bodies
  • Frontotemporal dementia
  • Neurodegenerative dementias
  • Neurofilament light
  • Parkinson's disease dementia
  • Prion diseases
  • Vascular dementia

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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