Do Tau-synaptic Long-term Depression Interactions in the Hippocampus Play a Pivotal Role in the Progression of Alzheimer's Disease?

Overview

Journal Neural Regen Res

Date 2022 Dec 1

PMID 36453396

Authors

Zhengtao Hu

Tomas Ondrejcak

Pengpeng Yu

Yangyang Zhang

Yin Yang

Igor Klyubin

Sean P Kennelly

Michael J Rowan

Neng-Wei Hu

Affiliations

Soon will be listed here.

Abstract

Cognitive decline in Alzheimer's disease correlates with the extent of tau pathology, in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus. Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-β or long-term depression, a form of synaptic weakening involved in learning and memory, share similar mechanisms. Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging. Conversely, certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau, in particular, phosphorylation at residue Ser396. Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau (hyper)phosphorylation. We first summarize experimental evidence regarding tau-long-term depression interactions, followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer's disease. Finally, we conclude with some thoughts and perspectives on future research about these interactions.

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