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Cerebrospinal fluid neurofilament light and tau protein as mortality biomarkers in parkinsonism
Author(s) -
Constantinescu Radu,
Rosengren Lars,
Eriksson Barbro,
Blennow Kaj,
Axelsson Markus
Publication year - 2019
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.13116
Subject(s) - progressive supranuclear palsy , amyotrophic lateral sclerosis , cerebrospinal fluid , medicine , corticobasal degeneration , synucleinopathies , parkinsonism , neurodegeneration , pathology , parkinson's disease , neurology , atrophy , tau protein , gastroenterology , alzheimer's disease , disease , alpha synuclein , psychiatry
Background Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF‐L), total tau (t‐tau), and the tau pathology marker phosphorylated tau (p‐tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders. Aims To investigate the CSF biomarkers' (NF‐L, t‐tau, and p‐tau) relationship to mortality in parkinsonian disorders. Methods Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors. Results NF‐L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196‐6.228, 95% confidence interval (CI)], P < 0.001), in PSP (HR 2.767 [1.126‐6.802 95% CI], P = 0.027), and in the entire cohort (HR 1.661 [1.082‐2.55, 95% CI], P = 0.02). t‐Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143‐80.418], P = 0.037). p‐Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041‐0.929, 95% CI], P = 0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516‐17.14, 95% CI] and HR 3.040 [1.904‐4.854], respectively, P < 0.001). Conclusion NF‐L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies.