Biological confounders for the values of cerebrospinal fluid proteins in Parkinson's disease and related disorders.

PMID:26452984
Mollenhauer B , Parnetti L , Rektorova I , Kramberger MG , Pikkarainen M , Schulz-Schaeffer WJ , Aarsland D , Svenningsson P , Farotti L , Verbeek MM , Schlossmacher MG
Journal of neurochemistry
Cerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. In Alzheimer's disease (AD), levels of increased CSF tau protein and decreased levels of β-amyloid 1-42 (Aβ42) have been shown to correlate with brain plaque formation and tangle pathology. Intracellular Lewy inclusions containing aggregated α-synuclein (α-syn) represent a pathological hallmark of Parkinson's disease (PD). In most-but not all-studies published to date total CSF α-syn concentrations have been found to be decreased in disorders related to α-syn pathology, i.e., PD, dementia with Lewy-bodies and multiple system atrophy. However, these reports show extensive signal overlap among tested individuals, thereby diminishing its potential for routine use in clinical practice. To investigate potential biological (i.e., non-technical) confounders of reported CSF levels for α-syn, Aβ42 and tau in PD and related disorders, we carried out a methodical review of known factors that underlie signal variability and speculate on those that have not yet been tested. We discuss several biological factors, such as neuropathology, demographics, clinical phenotype, progression and duration of disease, concomitant illnesses and, last but not least, pharmacotherapy, which in isolation or combination can substantially alter values for CSF proteins of interest. Enhanced implementation of standardized clinical protocols, streamlined operating procedures, and further progress in the development of validated assays for CSF proteins have the potential to (1) inform us as to the pathogenesis of disease, (2) support the laboratory-based diagnosis for symptomatic subjects in the future, and (3) facilitate breakthrough therapies to alter the course of neurodegenerative disorders, such as PD and AD. This article is protected by copyright. All rights reserved.


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