[18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation

J Neurol. 2018 May;265(5):1079-1088. doi: 10.1007/s00415-018-8815-x. Epub 2018 Mar 1.

Abstract

Corticobasal syndrome (CBS) is a phenotypic manifestation of diverse pathologies, including Alzheimer's disease and 4-repeat tauopathies. Predicting pathology in CBS is unreliable and, hence, molecular neuroimaging may prove to be useful. The aim of this study was to assess regional patterns of uptake on [18F] AV-1451 PET in CBS and determine whether patterns of uptake differ according to beta-amyloid deposition or differing clinical presentations. Fourteen patients meeting criteria for CBS underwent Pittsburgh Compound B (PiB) and [18F] AV-1451 PET. Seven patients presented as CBS and seven presented with apraxia of speech (AOS) and later evolved into CBS. A global PiB summary was calculated and used to classify patients as PiB (-) or PiB (+). AV-1451 uptake was calculated in fourteen regions-of-interest, with values divided by uptake in cerebellar crus grey matter to generate standard uptake value ratios. AV-1451 uptake was considered elevated if it fell above the 95th percentile from a group of 476 cognitively unimpaired normal controls. Six of the 14 CBS patients (43%) were PiB (+), with three of these patients showing strikingly elevated AV-1451 uptake across many cortical regions. Of the eight PiB (-) patients, only those with AOS showed elevated AV-1451 uptake in supplementary motor area and precentral cortex compared to controls. No region of elevated AV-1451 uptake were observed in PiB (-) typical CBS patients without AOS. These results suggest that regional [18F] AV-1451 is variable in CBS and depends on the presence of beta-amyloid as well as clinical presentation such as AOS. PiB (+) CBS does not necessarily reflect underlying Alzheimer's disease; however, the possibility some of these patients will evolve into Alzheimer's disease over time cannot be excluded.

Keywords: Alzheimer’s disease; Beta-amyloid; Corticobasal syndrome; Positron emission tomography; Tau.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Apraxias / diagnostic imaging
  • Apraxias / metabolism
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Brain Mapping
  • Carbolines*
  • Cohort Studies
  • Female
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / diagnostic imaging*
  • Neurodegenerative Diseases / metabolism
  • Positron-Emission Tomography*
  • Radiopharmaceuticals*
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Carbolines
  • Radiopharmaceuticals
  • Thiazoles
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole