Longitudinal amyloid-β PET in atypical Alzheimer's disease and frontotemporal lobar degeneration

Jennifer L. Whitwell, Nirubol Tosakulwong, Stephen D. Weigand, Jonathan Graff-Radford, Joseph R Duffy, Heather M. Clark, Mary M. Machulda, Hugo Botha, Rene L. Utianski, Christopher G. Schwarz, Matthew L. Senjem, Edythe Strand, Nilufer Ertekin-Taner, Clifford R. Jack, Val J. Lowe, Keith A. Josephs

Research output: Contribution to journalArticle

Abstract

Background: Rates of amyloid-β (Aβ) accumulation have been characterized across the cognitively normal to typical Alzheimer's dementia spectrum, but little is known about Aβ accumulation in atypical Alzheimer's disease (AD) and other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD). Objective: We aimed tocharacterize longitudinal Aβ accumulation anddetermine the influence of age, apolipoprotein E (APOE) genotype, disease duration, and sexin atypical AD and FTLD. Methods: 322 patients (138 atypical AD, 184 FTLD) underwent Pittsburgh compound B PET scanning, with 73 having serialPiB-PET scans (42 atypical AD, 31 FTLD). Global Aβ standard uptake value ratios were calculated for every scan. Mixed effects models were used to assess the effect of age, APOE genotype, disease duration, and sex on baseline and change measures of Aβ. Results: Atypical AD showed higher baseline Aβ than FTLD. Rate of Aβ accumulation was not associated with baseline Aβ in either group. Older age was associated with greater baseline Aβ and faster rates of accumulation in FTLD. In patients under age 70, atypical AD showed faster rates of accumulation than FTLD. APOE ϵ4 genotype was associated with greater baseline Aβ in FTLD but did not influence rates of accumulation. Rates of Aβ accumulation were faster in FTLD patents with time from onset-to-PET≤4 years. Female sex was associated with faster rates of accumulation in atypical AD. Conclusion: Accumulation of Aβ is observed in atypical AD and FTLD, although different demographic factors influence accumulation in these diseases providing insight into potentially different biological mechanisms of Aβ deposition.

Original languageEnglish (US)
Pages (from-to)377-389
Number of pages13
JournalJournal of Alzheimer's Disease
Volume74
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Alzheimer's disease
  • amyloid plaques
  • frontotemporal lobar degeneration
  • positron emission tomography

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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