Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates

Brittany Dugger, Christopher M. Clark, Geidy Serrano, Monica Mariner, Barry J. Bedell, R. Edward Coleman, P. Murali Doraiswamy, Ming Lu, Adam S. Fleisher, Eric M. Reiman, Marwan N. Sabbagh, Carl H. Sadowsky, Julie A. Schneider, Simone P. Zehntner, Alan P. Carpenter, Abhinay D. Joshi, Mark A. Mintun, Michael J. Pontecorvo, Daniel M. Skovronsky, Lucia I. SueThomas G. Beach

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume73
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Keywords

  • A-amyloid
  • Alzheimer disease
  • Argyrophilic grains
  • Autopsy
  • Cerebral amyloid angiopathy
  • Leuko-araiosis
  • Lewy bodies
  • PET imaging
  • Plaques
  • TDP-43
  • Vascular dementia
  • White matter.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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