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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
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Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Basic Science and Pathogenesis.

Ian Michael Oh1, Song Hua Li1, Felipe Luiz Pereira1

  • 1Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
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Summary
This summary is machine-generated.

Truncated tau (tr-tau) appears earlier than hyperphosphorylated tau (p-tau) in Alzheimer

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Area of Science:

  • Neuroscience
  • Pathology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) pathology is characterized by hyperphosphorylated tau (p-tau).
  • The role of other tau posttranslational modifications (PTMs), like caspase-6-truncated tau (tr-tau), is less understood.
  • tr-tau is prevalent in AD neurons, but its temporal relationship with p-tau is unclear.

Purpose of the Study:

  • To investigate the deposition patterns of tr-tau relative to p-tau throughout Alzheimer's disease progression.
  • To determine if tr-tau is an early pathological marker in AD.
  • To assess the colocalization of tr-tau and p-tau in affected brain regions.

Main Methods:

  • Analysis of 56 postmortem human brain tissue cases across all Braak stages (0-6).
  • Utilized multiplex immunofluorescence to detect tr-tau (D13, D402, TauC3) and p-tau (PHF1) species.
  • Quantified neuronal tau pathology and colocalization in the entorhinal cortex (EC) and inferior temporal gyrus (ITG).

Main Results:

  • D13 tr-tau was detected earlier than p-tau in both EC and ITG.
  • tr-tau burden exceeded p-tau burden in early Braak stages.
  • Minimal colocalization between tr-tau and p-tau was observed throughout disease progression.

Conclusions:

  • tr-tau emerges as an independent pathological feature in AD, preceding p-tau.
  • tr-tau represents a distinct early marker for Alzheimer's disease progression.
  • tr-tau is a potential novel therapeutic target for AD.