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Diagnostic approach to Argyrophilic Grain Disease (AGD): an UK BDR trial

Lookup NU author(s): Dr Claire Troakes, Professor Johannes Attems, Annette King, Professor Derek Mann

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Abstract

Introduction: AGD is a sporadic neurodegenerative disease of old age characterized by predominantly tau-4-repeat (tau4R)-positive argyrophilic grains in limbic areas of the brain. AGD may be underdiagnosed in the UK as diagnosis can be difficult, particularly if AGD co-exists with other neurodegenerative conditions. Our aim was to produce a harmonised diagnostic approach to AGD within the UK while keeping the assessment method simple. Material and methods: We selected 16 cases of different tauopathies from the archives of MRC London Neuro-degenerative Diseases Brain Bank. Sections of the hippocampus and amygdala were immunolabelled with hyperphosphorylated tau (AT8), p62, tau4R and tau3R antibodies. All 9 investigators were blinded to the diagnoses and initially received only AT8- and p62-labelled sections. Tau4R and tau3R sections were distributed in a second circulation. Tau positive structures, particularly grains, were scored semiquantitatively (0 to 3+) and the preferred diagnoses were given after each circulation. Results: At least 2+ tau-positive grains were recorded in 62% of all cases in the 1st circulation, but in only 50% after the additional tau4R and tau3R immunostains. Consequently, the preferred diagnosis of AGD decreased from 65% to 57%. Notably, the additional immunohistochemistry did not significantly change the evaluation of grains or the preferred diagnosis of AGD when AGD was present in pure form (6 cases). In those cases of tauopathy with additional neurodegenerative conditions (10 cases), at least 2+ tau-positive grains was noted in 48% in the 1st circulation but only in 30% when tau4R and tau3R preparations were examined; the preferred diagnosis of AGD decreased from 52% to 39%. Although the interobserver agreement was high in most instances, there were some caseswith poor agreement in the detection of grains, even after tau4R and tau3R immunolabelling. Conclusions: Generally, tau4R and tau3R immunolabelling enhances the confidence in diagnosing AGD particularly when it co-exists with other neurodegenerative conditions. However, in some cases the diagnosis of AGD remains problematic even on tau4R and tau3R immunolabelling.


Publication metadata

Author(s): Bodi I, Troakes C, Maekawa S, Attems J, Esiri MM, Hortobagyi T, King A, Love S, Mann D, Neal JW, Al-Sarraj S

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Proceedings of the 114th Meeting of the British Neuropathological Society, Institute of Child Health

Year of Conference: 2013

Pages: 9-9

ISSN: 0305-1846

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/j.1365-2990.2013.12029.x

DOI: 10.1111/j.1365-2990.2013.12029.x

Library holdings: Search Newcastle University Library for this item

Series Title: Neuropathology and Applied Neurobiology

ISBN:


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