Association of PTHrP levels in CSF with Alzheimer's disease biomarkers
Artikel i vetenskaplig tidskrift, 2019

Background: Parathyroid hormone-related protein (PTHrP) is involved in intracellular calcium regulation, neural cell proliferation and synaptic transmission. To date, no studies have been performed to evaluate the potential of PTHrP concentrations in cerebrospinal fluid (CSF) as a biomarker of brain pathophysiology. In this study we evaluated the association between CSF concentrations of PTHrP with the core CSF biomarkers of Alzheimer's disease (AD). Methods: PTHrP and calcium were analysed using validated mass spectrometry based methods in a set of CSF samples that tested positive (n=45) and negative (n=45) for the AD biomarkers, including total tau protein (T-tau), phosphorylated tau protein (P-tau) and amyloid-beta 42 (A beta 42). The measured CSF concentrations of PTHrP and calcium (Ca) were evaluated for association with AD CSF biomarkers. Results: PTHrP and Ca concentrations in CSF samples ranged between 25 and 137 pmol/L and 0.92-1.53 mmol/L, respectively. Higher concentrations of PTHrP were observed in association with increased concentrations of T-tau and P-tau in the AD and the control group; while a stronger correlation was observed in the control group (rho=0.6, p < 0.0001; and rho=0.72, p < 0.0001, for T-tau and P-tau, respectively). Negative correlation was observed between concentrations of PTHrP and A beta 42 in the AD group (rho=0.27, p=0.015). A statistically significantly lower ratio A beta 42/PTHrP was observed in the AD group (p < 0.0001). Conclusion: In the current study, we observed an association of PTHrP concentrations with concentrations of clinically used CSF biomarkers of AD. Concentrations of PTHrP were positively correlated with concentrations of T-tau and P-tau, suggesting an association with neuronal secretion and function, which is reduced upon progression to AD pathology. Our data suggest potential utility of the A beta 42/PTHrP ratio in assessment of AD progression.

Phosphorylated tau protein

Beta-amyloid

PTHrP

Tau protein

Parathyroid hormone-related protein

Alzheimer's disease

Mass spectrometry

Författare

Mark M. Kushnir

University of Utah

ARUP Institute for Clinical and Experimental Pathology

Wojciech Michno

Göteborgs universitet

Alan L. Rockwood

Rockwood Scientific Consulting

Kaj Blennow

Göteborgs universitet

Frederick G. Strathmann

NMS Labs

Jörg Hanrieder

Göteborgs universitet

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Clinical Mass Spectrometry

23769998 (eISSN)

Vol. 14 124-129

Ämneskategorier

Neurovetenskaper

Klinisk laboratoriemedicin

Neurologi

DOI

10.1016/j.clinms.2018.10.001

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Senast uppdaterat

2023-03-21