Tau and neurodegenerative disease: the story so far

Area of Science:

• Neuroscience
• Biochemistry
• Genetics

Background:

• Tau protein, initially identified in 1975, was later found to be the main component of neurofibrillary tangles in Alzheimer disease (AD).
• Abnormal hyperphosphorylation of tau in AD brains impairs microtubule assembly, contributing to disease pathology.
• While tau gene mutations are linked to frontotemporal dementia, they have not been identified in AD cases.

Purpose of the Study:

• To provide an overview of key discoveries in tau research over the past four decades.
• To review the current understanding of tau's role in disease mechanisms.
• To discuss emerging therapeutic strategies targeting tau.

Main Methods:

• Historical review of tau protein research and its connection to Alzheimer disease.
• Analysis of tau gene mutations in familial frontotemporal dementia.
• Overview of ongoing clinical trials and diagnostic assay development for tau.

Main Results:

• Tau protein is central to neurofibrillary tangle formation in Alzheimer disease.
• Hyperphosphorylated tau inhibits microtubule assembly, impacting neuronal function.
• Significant progress has been made in developing tau-based diagnostics and therapeutics, including vaccines.

Conclusions:

• Tau protein is a critical factor in Alzheimer disease pathogenesis.
• The field has advanced significantly, with new diagnostic tools and therapeutic interventions under development.
• Targeting tau represents a promising avenue for future Alzheimer disease treatments.