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. 2019 Sep 20;20(19):4661.
doi: 10.3390/ijms20194661.

The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer's Disease (AD)

Barbara Mroczko  1   2 , Magdalena Groblewska  3 , Ala Litman-Zawadzka  4
Affiliations

The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer's Disease (AD)

Barbara Mroczko et al. Int J Mol Sci. .

Abstract

Although the causative role of the accumulation of amyloid β 1-42 (Aβ42) deposits in the pathogenesis of Alzheimer's disease (AD) has been under debate for many years, it is supposed that the toxicity soluble oligomers of Tau protein (TauOs) might be also the pathogenic factor acting on the initial stages of this disease. Therefore, we performed a thorough search for literature pertaining to our investigation via the MEDLINE/PubMed database. It was shown that soluble TauOs, especially granular forms, may be the most toxic form of this protein. Hyperphosphorylated TauOs can reduce the number of synapses by missorting into axonal compartments of neurons other than axon. Furthermore, soluble TauOs may be also responsible for seeding Tau pathology within AD brains, with probable link to AβOs toxicity. Additionally, the concentrations of TauOs in the cerebrospinal fluid (CSF) and plasma of AD patients were higher than in non-demented controls, and revealed a negative correlation with mini-mental state examination (MMSE) scores. It was postulated that adding the measurements of TauOs to the panel of CSF biomarkers could improve the diagnosis of AD.

Keywords: Alzheimer′s disease; CSF; neurodegeneration; plasma; protein misfolding; serum; tau oligomers; tauopathy.

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Conflict of interest statement

B.M. has received consultation and/or lecture honoraria from Abbott, Roche, Cormay and Biameditek.

Figures

Figure 1
Figure 1
Schematic illustration of articles included in the review manuscript [31].
Figure 2
Figure 2
Schematic structure of Tau molecule in central (CNS) and peripheral nervous system (PNS) in relation to alternative splicing of exons. Abbreviations; PRD—proline rich domain, MBD—microtubule binding domain, AA—aminoacids.
See this image and copyright information in PMC

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