ArticleAging cell2018
Acute tau knockdown in the hippocampus of adult mice causes learning and memory deficits.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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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.
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Who cites it
59 citing papers in PubMed, 108 citations in OpenAlex.
- Elevated DYRK1A in Primary Tauopathies and Therapeutic Targeting with the Brain-Penetrant Inhibitor DYR533.Research square · 2026Article
- Elimination of tau tangles and soluble aggregates with the small molecule ACI-16664 prevents neurodegeneration in vivo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- miR-125b Mediates Tau-induced Mitochondrial Dysfunction in a Cellular Model of Alzheimer's Disease.Molecular neurobiology · 2026Article
- Beyond microtubule regulation: the multifaceted roles of tau in neuronal function and dysfunction.Translational psychiatry · 2026Review
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Multi-omic phenotyping of MAPT V337M neurons reveals early changes in axonogenesis and tau phosphorylation.NPJ dementia · 2026Article
- Adult-onset hippocampal α7 nicotinic acetylcholine receptor loss rapidly drives Alzheimer-like neuropathology in mice.Frontiers in pharmacology · 2026Article
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Health effects of loss of function variants in gene targets for Alzheimer's disease prevention.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Structure and mechanism of microtubule stabilization and motor regulation by MAP9.bioRxiv : the preprint server for biology · 2025Article
- Preclinical Development of a Vectorized Artificial miRNA Gene Therapy for Tauopathies.bioRxiv : the preprint server for biology · 2025Article
- Multi-omic phenotyping of iPSC-derived neurons harboring thebioRxiv : the preprint server for biology · 2025Article
- Axonal tau reduction ameliorates tau and amyloid pathology in a mouse model of Alzheimer's disease.Translational neurodegeneration · 2025Article
- Brain Neurotrophins and Plant Polyphenols: A Powerful Connection.Molecules (Basel, Switzerland) · 2025Review
- ApoE Isoform-Dependent Effects on Extinction of Contextual Fear Memory and Passive Avoidance Memory.International journal of molecular sciences · 2025Article
- The Unified Theory of Neurodegeneration Pathogenesis Based on Axon Deamidation.International journal of molecular sciences · 2025Review
- Targeting USP11 regulation by a novel lithium-organic coordination compound improves neuropathologies and cognitive functions in Alzheimer transgenic mice.EMBO molecular medicine · 2024Article
- Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.Nature neuroscience · 2024Article
- Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer's Disease and Other Tauopathies.Molecular neurobiology · 2024Review
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Misfolded and hyperphosphorylated tau accumulates in several neurodegenerative disorders including Alzheimer's disease, frontotemporal dementia with Parkinsonism, corticobasal degeneration, progressive supranuclear palsy, Down syndrome, and Pick's disease. Tau is a microtubule-binding protein, and its role in microtubule stabilization is well defined. In contrast, while growing evidence suggests that tau is also involved in synaptic physiology, a complete assessment of tau function in the adult brain has been hampered by robust developmental compensation of other microtubule-binding proteins in tau knockout mice. To circumvent these developmental compensations and assess the role of tau in the adult brain, we generated an adeno-associated virus (AAV) expressing a doxycycline-inducible short-hairpin (Sh) RNA targeted to tau, herein referred to as AAV-ShRNATau. We performed bilateral stereotaxic injections in 7-month-old C57Bl6/SJL wild-type mice with either the AAV-ShRNATau or a control AAV. We found that acute knockdown of tau in the adult hippocampus significantly impaired motor coordination and spatial memory. Blocking the expression of the AAV-ShRNATau, thereby allowing tau levels to return to control levels, restored motor coordination and spatial memory. Mechanistically, the reduced tau levels were associated with lower BDNF levels, reduced levels of synaptic proteins associated with learning, and decreased spine density. We provide compelling evidence that tau is necessary for motor and cognitive function in the adult brain, thereby firmly supporting that tau loss-of-function may contribute to the clinical manifestations of many tauopathies. These findings have profound clinical implications given that anti-tau therapies are in clinical trials for Alzheimer's disease.
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What Socratic 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 Socratic graph.