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Supplementary material from "Rapidly reversible persistent LTP inhibition by patient-derived brain tau and amyloid ß proteins"

Version 2 2024-06-03, 11:37
Version 1 2024-04-26, 15:53
Posted on 2024-06-03 - 11:37
How the two pathognomonic proteins of Alzheimer’s disease, amyloid ß (Aß) and tau, cause synaptic failure remains enigmatic. Certain synthetic and recombinant forms of these proteins are known to act concurrently to acutely inhibit LTP. Here we examined the effect of early amyloidosis on the acute disruptive action of synaptotoxic tau prepared from recombinant protein and tau in patient-derived aqueous brain extracts. We also explored the persistence of the inhibition of LTP by different synaptotoxic tau preparations. A single intracerebral injection of aggregates of recombinant human tau that had been prepared by either sonication of fibrils (SτAs) or disulfide bond formation (oTau) rapidly and persistently inhibited LTP in rat hippocampus. The threshold for the acute inhibitory effect of oTau was lowered in APP transgenic rats. A single injection of synaptotoxic tau-containing Alzheimer's disease or Pick’s disease brain extracts also inhibited LTP, for over two weeks. Remarkably, the persistent disruption of synaptic plasticity by patient-derived brain tau was rapidly reversed by a single intracerebral injection of different anti-tau monoclonal antibodies, including one directed to a specific human tau amino acid sequence. We conclude that patient-derived LTP-disrupting tau species persist in the brain for weeks, maintaining their neuroactivity often in concert with Aß.

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Philosophical Transactions of the Royal Society B: Biological Sciences

AUTHORS (7)

Tomas Ondrejcak
Igor Klyubin
Neng-Wei Hu
Yin Yang
Qiancheng Zhang
B. J. Rodriguez
Michael Rowan

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