Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injectionReportar como inadecuado

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Acta Neuropathologica Communications

, 4:130

First Online: 12 December 2016Received: 16 November 2016Accepted: 29 November 2016


In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer’s disease AD, aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of Fflutemetamol positron emission tomography PET imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups. The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of Fflutemetamol PET by majority read for the presence of moderate or frequent plaques. The probability of an abnormal Fflutemetamol scan increased with neocortical plaque density and AD diagnosis. All dementia cases with non-AD neurodegenerative diseases and those without histopathological features of β-amyloid deposits were Fflutemetamol negative. Majority PET assessments accurately reflected the amyloid plaque burden in 90% of cases. However, ten cases demonstrated a mismatch between PET image interpretations and post-mortem findings. Although tracer retention was best associated with amyloid in neuritic plaques, amyloid in diffuse plaques and cerebral amyloid angiopathy best explain three Fflutemetamol positive cases with mismatched sparse neuritic plaque burden. Advanced cortical atrophy was associated with the seven false negative Fflutemetamol images. The interpretation of images from pathologically equivocal cases was associated with low reader confidence and inter-reader agreement. Our results support that amyloid in neuritic plaque burden is the primary form of β-amyloid pathology detectable with Fflutemetamol PET imaging. NCT01165554. Registered June 21, 2010; NCT02090855. Registered March 11, 2014.

KeywordsFlutemetamol PET Amyloid Alzheimer’s disease Neuropathology 4-6 allowed Electronic supplementary materialThe online version of this article doi:10.1186-s40478-016-0399-z contains supplementary material, which is available to authorized users.

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Autor: Milos D. Ikonomovic - Chris J. Buckley - Kerstin Heurling - Paul Sherwin - Paul A. Jones - Michelle Zanette - Chester A.


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