Toggle Main Menu Toggle Search

Open Access padlockePrints

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 WalkerORCiD, Dr Daniel ErskineORCiD, Mary Johnson, Dr David KossORCiD, Professor Alan ThomasORCiD, Professor Johannes Attems


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


© 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. Aims: 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: John Wiley & Sons Ltd


DOI: 10.1111/nan.12664

PubMed id: 32896913


Altmetrics provided by Altmetric