Chronic effects of inflammation on tauopathies

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

Review

Chronic effects of inflammation on tauopathies

Connor Langworth-Green et al. Lancet Neurol. 2023 May.

. 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.

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Conflict of interest statement

Declaration of interests MZ received an honorarium for a lecture to UCB Pharma in December, 2019, and has received support for attending a European Academy of Neurology Encephalitis workshop meeting in April, 2022. MZ receives salary support for research time from the University College London Hospitals NHS Foundation Trust National Institute for Health and Care Research Biomedical Research Centre. HM is funded by grants from Parkinson's UK, the Michael J Fox Foundation, the PSP Association, CBD solutions, and the Drake Foundation. Unrelated to the current work, HM receives consulting fees from Roche and Amylyx. HM has received personal lecture fees from Kyowa Kirin, the British medical journal, and the Movement Disorders Society. HM is a co-applicant on a patent application related to C9ORF72—method for diagnosing a neurodegenerative disease (PCT/GB2012/052140). HM is on the advisory board for the CurePSP association, the Association of British Neurologists Movement Disorders Special Interest Group, and the Association of British Neurologists Neurogenetics Advisory Group, all of which are unrelated to this work. EJ has received research funding from the UK Medical Research Council, PSP Association, and CurePSP association. JH and KD receive support and grants from the UK Dementia Research Institute (Medical Research Council, the Alzheimer's Society and Alzheimer's Research UK). JH is a recipient of a grant from the Dolby foundation. JH and KD consult and hold stock options for Ceracuity, a startup, which currently has no drugs on the market. JH has received payment for lectures and consults for Eli Lilly, Eisai, and Merck. KD is a recipient of grants from the National Institutes of Health and Cure Alzheimer's fund. KD has received royalties or licences from University South Florida, the Research foundation for mental hygiene, and Rainwater charitable fund. KD has received payment from academic institutions for keynote and plenary talks. KD has patents relating to an amyloid precursor protein mice and humanised tau mouse models.

Comment in

Chronic inflammation: a potential target in tauopathies.
Ising C, Heneka MT. Ising C, et al. Lancet Neurol. 2023 May;22(5):371-373. doi: 10.1016/S1474-4422(23)00116-3. Lancet Neurol. 2023. PMID: 37059499 No abstract available.

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Chronic effects of inflammation on tauopathies

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Chronic effects of inflammation on tauopathies

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