Research Article: Metabolic status of CSF distinguishes rats with tauopathy from controls

Date Published: September 21, 2017

Publisher: BioMed Central

Author(s): Radana Karlíková, Kateřina Mičová, Lukáš Najdekr, Alžběta Gardlo, Tomáš Adam, Petra Majerová, David Friedecký, Andrej Kováč.


Tauopathies represent heterogeneous groups of neurodegenerative diseases that are characterised by abnormal deposition of the microtubule-associated protein tau. Alzheimer’s disease is the most prevalent tauopathy, affecting more than 35 million people worldwide. In this study we investigated changes in metabolic pathways associated with tau-induced neurodegeneration.

Cerebrospinal fluid (CSF), plasma and brain tissue were collected from a transgenic rat model for tauopathies and from age-matched control animals. The samples were analysed by targeted and untargeted metabolomic methods using high-performance liquid chromatography coupled to mass spectrometry. Unsupervised and supervised statistical analysis revealed biochemical changes associated with the tauopathy process.

Energy deprivation and potentially neural apoptosis were reflected in increased purine nucleotide catabolism and decreased levels of citric acid cycle intermediates and glucose. However, in CSF, increased levels of citrate and aconitate that can be attributed to glial activation were observed. Other significant changes were found in arginine and phosphatidylcholine metabolism.

Despite an enormous effort invested in development of biomarkers for tauopathies during the last 20 years, there is no clinically used biomarker or assay on the market. One of the most promising strategies is to create a panel of markers (e.g., small molecules, proteins) that will be continuously monitored and correlated with patients’ clinical outcome. In this study, we identified several metabolic changes that are affected during the tauopathy process and may be considered as potential markers of tauopathies in humans.

The online version of this article (doi:10.1186/s13195-017-0303-5) contains supplementary material, which is available to authorized users.

Partial Text

Tauopathies include around 20 different degenerative disorders, such as Alzheimer’s disease (AD), progressive supranuclear palsy, Pick’s disease, corticobasal degeneration, frontotemporal dementia with Parkinsonism linked to chromosome 17, dementia pugilistica/traumatic brain injury/chronic traumatic encephalopathy complex, and others. According to the pathology, we divide tauopathies into three main groups: tauopathies associated with the deposition-predominant tau pathology composed mainly of abnormal deposition of tau into intracellular neurofibrillary tangles, tauopathies associated with the deposition of amyloid beta (Aβ), and tauopathies associated with other pathologies [1].

Progressive neurofibrillary pathology in Tg rats was induced by expression of truncated tau, which consists of four microtubule-binding domains (4R) and a proline-rich region (151–391/4R). Neurofibrillary degeneration in these animals displays biochemical and histopathological features similar to those of human tau neurodegeneration, such as extensive formation of detergent-insoluble tau protein complexes and thioflavin S reactivity.

We have identified several metabolic changes affected by the tauopathy process that may be considered as potential markers for diagnosis of tauopathies in humans. Moreover, some of the identified pathways have previously been reported to be connected to neurodegeneration. We thus believe that detailed understanding of molecular processes behind the changes can lead to development of specific analytical methods and ultimately to monitoring of these features in ongoing anti-tau clinical trials.




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