ArticleActa neuropathologica communications2021
P62 accumulates through neuroanatomical circuits in response to tauopathy propagation.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
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- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Diagnostic Utility of Vestibular Markers in Identifying Mild Cognitive Impairment and Early Alzheimer's Disease in Older Adults.Journal of clinical medicine · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Human MAPT knockin mouse models of frontotemporal dementia for the neurodegenerative research community.Cell reports methods · 2025Article
- Understanding retinal tau pathology through functional 2D and 3D iPSC-derived in vitro retinal models.Acta neuropathologica communications · 2025Article
- Proteomic signatures of Alzheimer's disease and Lewy body dementias: A comparative analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The influence of APOEActa neuropathologica · 2024Article
- The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Precision proteoform design for 4R tau isoform selective templated aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Precision Proteoform Design for 4R Tau Isoform Selective Templated Aggregation.bioRxiv : the preprint server for biology · 2023Article
- Multiomic prediction of therapeutic targets for human diseases associated with protein phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Survival in sporadic ALS is associated with lower p62 burden in the spinal cord.Journal of neuropathology and experimental neurology · 2023Article
- Shu-Xie decoction alleviates oxidative stress and colon injury in acute sleep-deprived mice by suppressing p62/KEAP1/NRF2/HO1/NQO1 signaling.Frontiers in pharmacology · 2023Article
- Investigating p62 Concentrations in Cerebrospinal Fluid of Patients with Dementia: A Potential Autophagy Biomarker In Vivo?Brain sciences · 2022Article
- Tau interactome and RNA binding proteins in neurodegenerative diseases.Molecular neurodegeneration · 2022Review
- Tau seeding in cases of multiple sclerosis.Acta neuropathologica communications · 2022Article
- Interplay between exosomes and autophagy machinery in pain management: State of the art.Neurobiology of pain (Cambridge, Mass.)Article
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
In Alzheimer's disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.
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