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Concomitant LATE-NC in Alzheimer's disease is not associated with increased tau or amyloid-β pathological burden

Lookup NU author(s): Dr Kirsty McAleese, Dr Lauren Walker, Dr Daniel Erskine, Mary Johnson, Dr David Koss, Professor Alan Thomas, Professor Johannes Attems

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Abstract

© 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological SocietyAims: Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is present in approximately 50% of Alzheimer's disease (AD) cases and is associated with accelerated cognitive decline. Studies indicate a potential synergistic relationship between LATE-NC and hyperphosphorylated tau. It is unknown if LATE-NC is an independent driver of cognitive impairment or exerts its influence through synergistic relationships with tau. This cliniconeuropathological study investigated the impact of LATE-NC on quantified measures of AD-associated pathology and its impact on clinical measures. Methods: A total of 61 AD cases underwent neuropathological assessment for LATE-NC and quantitative assessment [area covered by immunoreactivity (IR)] for early conformational tau (MC-1), late-stage hyperphosphorylated tau (AT8) and amyloid-β in the amygdala and five neocortical regions. Clinical measures included age of disease onset, final Mini-Mental State Examination (MMSE) score and rate of cognitive decline. Results: LATE-NC was present in 41 AD cases (AD/LATE-NC; 67.2%). No significant differences in MC-1-IR, AT8-IR or 4G8-IR were observed in any region between AD/LATE-NC and AD without LATE-NC, indicating no accelerated aggregation or hyperphosphorylation of tau proteins in the AD/LATE-NC cases. Final MMSE was significantly lower in AD/LATE-NC cases and was significantly associated with LATE-NC score even when controlled for the presence of both MC-1-IR and AT8-IR (P = 0.009). Conclusion: The presence of LATE-NC in AD is not associated with an increase in the burden of early or late tau or Aβ pathology. LATE-NC is associated with a lower final MMSE score independent of tau pathology.


Publication metadata

Author(s): McAleese KE, Walker L, Erskine D, Johnson M, Koss D, Thomas AJ, Attems J

Publication type: Article

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2020

Volume: 46

Issue: 7

Pages: 722-734

Print publication date: 01/12/2020

Online publication date: 08/09/2020

Acceptance date: 22/08/2020

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Blackwell Publishing Ltd

URL: https://doi.org/10.1111/nan.12664

DOI: 10.1111/nan.12664

PubMed id: 32896913


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