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Miki Murota1, Roberta Tufi2, Naoki Tokuhara1

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Summary
This summary is machine-generated.

The antibody E2814 reduces neuronal tau uptake and enhances microglial clearance, potentially slowing the spread of tau pathology in neurodegenerative diseases like Alzheimer's disease (AD).

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Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Tau deposition is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD).
  • Pathological tau spreads via connected pathways, with microtubule-binding region (MTBR) tau forming seeds.
  • E2814 is an antibody targeting tau-MTBR in clinical trials to prevent tau pathology spread.

Purpose of the Study:

  • Investigate the mechanism of E2814 and 7G6 in cellular tau uptake.
  • Assess the impact of these antibodies on neuronal and microglial tau internalization.

Main Methods:

  • Utilized in vitro cultures of rodent and human neurons (iPSC-derived glutamatergic).
  • Isolated and cultured primary and iPSC-derived microglia.
  • Measured intracellular tau using fluorescently labeled tau, antibodies, and live cell imaging.

Main Results:

  • E2814 and 7G6 decreased tau uptake in both rodent and human neurons.
  • Microglial tau uptake increased in the presence of the antibody, dependent on effector function.

Conclusions:

  • E2814 may impede tau pathology spread by inhibiting neuronal tau uptake.
  • The antibody may also accelerate MTBR-tau clearance through microglial pathways.