RT Journal Article
SR Electronic
T1 CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 1117
OP 1123
DO 10.1136/jnnp-2019-320826
VO 90
IS 10
A1 Anna Jeppsson
A1 Carsten Wikkelsö
A1 Kaj Blennow
A1 Henrik Zetterberg
A1 Radu Constantinescu
A1 Anne M Remes
A1 Sanna-Kaisa Herukka
A1 Tuomas Rauramaa
A1 Katarina Nagga
A1 Ville Leinonen
A1 Mats Tullberg
YR 2019
UL http://jnnp.bmj.com/content/90/10/1117.abstract
AB Objective To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer’s disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders.Methods The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson’s disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer’s disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1).Results Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers.Conclusions The combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.