Tau-mediated Neurodegeneration and Potential Implications in Diagnosis and Treatment of Alzheimer's Disease

Dec 15, 2017Chinese medical journal

Brain cell damage linked to tau protein and its possible role in diagnosing and treating Alzheimer's disease

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Abstract

Recent advances highlight tau as a potential therapeutic target and biomarker for Alzheimer's disease (AD).

Amyloid plaques and neurofibrillary tangles made of hyperphosphorylated tau are key features of AD.
Clinical strategies targeting amyloid beta have not effectively treated or prevented AD onset.
Research is increasingly focusing on tau's role in AD pathogenesis, alongside its phosphorylation, acetylation, and cleavage.
New methods for detecting tau in cerebrospinal fluid and blood have been developed, enabling early diagnosis.
Improved imaging tracers are enhancing the ability to visualize tau in the brain.
Targeting tau pathology may offer new avenues for AD treatment through anti-tau immunotherapy.

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OBJECTIVE: To review recent research advances on tau, a major player in Alzheimer's disease (AD) pathogenesis, a biomarker for AD onset, and potential target for AD therapy.

DATA SOURCES: This review was based on a comprehensive search using online literature databases, including PubMed, Web of Science, and Google Scholar.

STUDY SELECTION: Literature search was based on the following keywords: Alzheimer's disease, tau protein, biomarker, cerebrospinal fluid (CSF), therapeutics, plasma, imaging, propagation, spreading, seeding, prion, conformational templating, and posttranslational modification. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.

RESULTS: Amyloid plaques enriched with extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks of AD. Although the Aβ hypothesis has dominated AD research for many years, clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset. The research focus in AD has recently shifted to the role of tau in AD. In addition to phosphorylation, tau is acetylated and proteolytically cleaved, which also contribute to its physiological and pathological functions. Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis. Techniques to detect tau at minute levels in CSF and blood have been developed, and improved tracers have facilitated tau imaging in the brain. These advances have potential to accurately determine tau levels at early diagnostic stages in AD. Given that tau is a potential therapeutic target, anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.

CONCLUSION: Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.

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Tau-mediated Neurodegeneration and Potential Implications in Diagnosis and Treatment of Alzheimer's Disease

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