ArticleActa neuropathologica2017
Hyperphosphorylated tau causes reduced hippocampal CA1 excitability by relocating the axon initial segment.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
99 citing papers in PubMed, 158 citations in OpenAlex.
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Aberrant tau accumulation caused by MAPT mutations induces early pathological changes in axonal transport that are rescued by p38α inhibition.Nature neuroscience · 2026Article
- Calbindin-D28k deficiency mediates tau-driven hippocampal hyperexcitement and cognitive impairment.Translational neurodegeneration · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Regional correlates of tau pathology and synaptic function in primary age-related tauopathy.Journal of Alzheimer's disease : JAD · 2026Article
- Selective vulnerability of human synapses to soluble tau oligomers.Journal of Alzheimer's disease : JAD · 2026Article
- Drosophila wing is a high-throughput and versatile screening tool for Tau-mediated disease mechanisms and drug discovery.Disease models & mechanisms · 2026Article
- Excitation-inhibition homeostasis in Alzheimer's disease: a selective multiscale review of mechanisms, sex differences, and therapeutic opportunities.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Cerebrospinal Fluid, Plasma Tryptophan, Kynurenine, and Kynurenate with Sleep Phenotypes: A Bidirectional Mendelian Randomization Analysis.International journal of tryptophan research : IJTR · 2026Article
- Pathological tau alters head direction signaling and induces spatial disorientation.Cell reports · 2025Article
- Endoplasmic Reticulum Stress Mediates Axon Initial Segment Shortening: Implications for Diabetic Brain Complications.Journal of molecular neuroscience : MN · 2025Article
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Understanding Tau pathology: Insights from animal models.Zoological research · 2025Review
- Neurons ensheathed by perineuronal nets are prone to hyperphosphorylation of tau protein in the hibernating Syrian hamster brain.Scientific reports · 2025Article
- Distinct manifestations of excitatory-inhibitory imbalance associated with amyloid-β and tau in patients with Alzheimer's disease.Nature communications · 2025Article
- Tau conveys intrinsic hyperactivity of VTA dopamine neurons but an inability to sustain burst firing.bioRxiv : the preprint server for biology · 2025Article
- Polycyclitol Derivatives Restore Long- Term Memory Via cdk5/p25 Activation of Tau Signaling in Experimental Cerebral Malaria.Neurochemical research · 2025Article
- Axon initial segment structure and function in health and disease.Physiological reviews · 2025Review
- Longitudinal excitation-inhibition balance altered by sex and APOE-ε4.Communications biology · 2025Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperphosphorylated tau has a critical role in tauopathies such as Alzheimer's disease and frontotemporal dementia, impairing neuronal function and eventually leading to neurodegeneration. A critical role for tau is supported by studies in transgenic mouse models that express the P301L tau mutation found in cases of familial frontotemporal dementia, with the accumulation of hyperphosphorylated tau in the hippocampus causing reductions in hippocampal long-term potentiation and impairments in spatial learning and memory. However, what has remained unexplored is the role of hyperphosphorylated tau in reducing neuronal excitability. Here, we show in two complementary P301L tau transgenic mouse models that hyperphosphorylated tau induces a more depolarized threshold for action potential initiation and reduces firing in hippocampal CA1 neurons, which was rescued by the suppression of transgenic tau. Furthermore, using mutagenesis and primary hippocampal neuronal cultures, we reveal that this reduction in neuronal excitability results from the relocation of the axon initial segment (AIS) down the axon in a tau phosphorylation-dependent manner. We also demonstrate that this effect is microtubule-dependent. In addition, pharmacological stabilization was found to prevent both the structural and functional deficits caused by tau hyperphosphorylation. Finally, we demonstrate that the AIS of neurons from tau transgenic mice is further down the axon, which correlates with a reduction in excitability. We therefore propose that a reduction in hippocampal excitability due to a tau-mediated distal relocalization of the AIS contributes to the hippocampal dysfunction observed in tauopathies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.