Dataset Information

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

ABSTRACT: Although the causative role of the accumulation of amyloid ? 1-42 (A?42) 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 A?Os 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.

SUBMITTER: Mroczko B

PROVIDER: S-EPMC6802364 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Mroczko Barbara B Groblewska Magdalena M Litman-Zawadzka Ala A

International journal of molecular sciences 20190920 19

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 f ...[more]

PMID: 31547024

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Project description:Pathological tau aggregates in Alzheimer's disease (AD) and frontotemporal lobar degeneration-tau (FTLD-tau) adopt distinct conformations differentiated by the AD-tau specific monoclonal antibody (mAb) GT-38 that are not readily visualized using phosphorylation-specific anti-tau mAbs. To determine the extent of co-morbid AD-tau pathology in FTLD-tau, we performed immunohistochemical (IHC) staining with GT-38 and assigned Braak stages of AD-tau in a cohort 180 FTLD-tau cases consisting of corticobasal degeneration (CBD; n?=?49), progressive supranuclear palsy (PSP; n?=?109), and Pick's disease (PiD; n?=?22). Nearly two-thirds of patients (n?=?115 of 180, 63.8%) with FTLD-tau had some degree of comorbid AD-tau pathology and 20.5% of the FTLD-tau cohort had Braak stage ?B2, consistent with medium-to-high-level AD neuropathological change (ADNPC). The PSP group had the highest frequency of medium-high AD-tau pathology compared to other tauopathies (PSP?=?31/109, 28.4%; Picks?=?2/22, 9.1%, CBD?=?4/49, 8.2%) but neuropathological diagnosis was not found to be a significant independent predictor of medium-high AD Braak stage in a multivariate model after accounting for age at death (OR?=?1.09; 95% CI?=?1.03-1.15; p?=?0.002) and CERAD plaque scores (OR?=?3.75, 95% CI?=?1.58-8.89; p?=?0.003), suggesting there is no predilection for a specific FTLD tauopathy to develop AD-tau co-pathology after accounting for age. Patients with FTLD-tau who had, clinically significant, medium-high AD-tau pathology had significantly higher antemortem CSF levels of both total-tau (t-tau; mean?=?89.98?pg/ml, SD?=?36.70?pg/ml) and phosphorylated-tau (p-tau; mean?=?20.45?pg/ml, SD?=?9.31?pg/ml) compared to patients with negligible-low AD-tau, t-tau (mean?=?43.04?pg/ml, SD?=?25.40?pg/ml) and p-tau (mean?=?11.90?pg/ml, SD?=?4.48?pg/ml) (p???0.001 both). Finally, in an exploratory analysis in our largest pathology group (PSP) we find an association of GT-38?AD-tau Braak stage with lower baseline MMSE (p?=?0.03). Together, these finding validate the use of GT-38 to selectively detect AD-tau pathology in the context of FTLD-tau and provides a novel tool to investigate associations of clinical phenotypes amongst co-morbid tauopathies.

Dataset Information

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

Publications

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

Similar Datasets

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