Unraveling tau's fold: Structural dynamics in Alzheimer's pathogenesis

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Alzheimer's disease (AD) is the most common dementia, affecting over 55 million globally, with two-thirds being women.
• AD is a progressive neurodegenerative disorder where pathological changes begin 15-20 years before clinical symptoms manifest.
• Key pathological hallmarks include neurofibrillary tangles (NFTs) and neuritic plaques.

Purpose of the Study:

• To describe neurofibrillary tangles (NFTs) and their composition.
• To focus on the pathological processing of tau protein, specifically truncation at Glu391.
• To investigate the role of tau truncation as an early biomarker for Alzheimer's disease.

Main Methods:

• Histopathological analysis of NFTs.
• Examination of tau protein post-translational modifications, including hyperphosphorylation and truncation.
• Review of existing reports and presentation of new evidence.

Main Results:

• NFTs are composed of paired helical filaments of tau protein.
• Tau protein undergoes modifications like hyperphosphorylation and truncation, leading to conformational changes.
• Truncation at Glu391 (PHF-core) is identified as a key pathological event and an early AD biomarker.

Conclusions:

• The study highlights tau protein truncation at Glu391 as a critical pathological event in AD.
• Hyperphosphorylated tau protein may act as a neuroprotective mechanism against the toxic PHF-core.
• Further research into tau pathology could yield early diagnostic tools and therapeutic targets for Alzheimer's disease.