Chronic effects of inflammation on tauopathies

Connor Langworth-Green; Saisha Patel; Zane Jaunmuktane; Edwin Jabbari; Huw Morris; Maria Thom; Andrew Lees; John Hardy; Michael Zandi; Karen Duff

doi:10.1016/S1474-4422(23)00038-8

Chronic effects of inflammation on tauopathies

Lancet Neurol. 2023 May;22(5):430-442. doi: 10.1016/S1474-4422(23)00038-8.

Authors

Connor Langworth-Green¹, Saisha Patel², Zane Jaunmuktane³, Edwin Jabbari⁴, Huw Morris⁴, Maria Thom⁵, Andrew Lees⁶, John Hardy⁷, Michael Zandi⁸, Karen Duff⁹

Affiliations

¹ University College London Medical School, University College London, London, UK.
² UK Dementia Research Institute, University College London, London, UK.
³ Department of Clinical and Movement Neurosciences, University College London, London, UK; Queen Square Brain Bank for Neurological Disorders, University College London, London, UK; Division of Neuropathology, University College London, London, UK; National Hospital for Neurology and Neurosurgery, London, UK.
⁴ Department of Clinical and Movement Neurosciences, University College London, London, UK; National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurology, Royal Free Hospital, London, UK.
⁵ Division of Neuropathology, University College London, London, UK; Department of Clinical and Experimental Epilepsy, University College London, London, UK.
⁶ Department of Clinical and Movement Neurosciences, University College London, London, UK; Reta Lila Weston Institute, University College London, London, UK.
⁷ UK Dementia Research Institute, University College London, London, UK; Reta Lila Weston Institute, University College London, London, UK; Department of Neurodegenerative Disease, University College London, London, UK.
⁸ Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK; National Hospital for Neurology and Neurosurgery, London, UK.
⁹ UK Dementia Research Institute, University College London, London, UK. Electronic address: k.duff@ucl.ac.uk.

PMID: 37059510
DOI: 10.1016/S1474-4422(23)00038-8

Abstract

Tauopathies are a heterogeneous group of neurodegenerative disorders that are characterised by the aggregation of the microtubule-associated protein tau into filamentous inclusions within neurons and glia. Alzheimer's disease is the most prevalent tauopathy. Despite years of intense research efforts, developing disease-modifying interventions for these disorders has been very challenging. The detrimental role that chronic inflammation plays in the pathogenesis of Alzheimer's disease is increasingly recognised; however, it is largely ascribed to the accumulation of amyloid β, leaving the effect of chronic inflammation on tau pathology and neurofibrillary tangle-related pathways greatly overlooked. Tau pathology can independently arise secondary to a range of triggers that are each associated with inflammatory processes, including infection, repetitive mild traumatic brain injury, seizure activity, and autoimmune disease. A greater understanding of the chronic effects of inflammation on the development and progression of tauopathies could help forge a path for the establishment of effective immunomodulatory disease-modifying interventions for clinical use.

Publication types

Review

MeSH terms

Alzheimer Disease* / pathology
Amyloid beta-Peptides / metabolism
Brain / pathology
Humans
Inflammation / metabolism
Tauopathies*
tau Proteins / metabolism

Substances

Amyloid beta-Peptides
tau Proteins