Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease

Research output: Contribution to journalArticle

Abstract

Objective: The clinical phenotype of the rare behavioural variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination. Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardised (W-)scores, adjusting for age, sex and mini mental state examination in a 'typical' memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed patients with bvAD (n=8) and typical AD (tAD;n=7). Results: Individual regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, that is, case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the tAD group. Postmortem AT8 staining indicated no group-level regional differences in phosphorylated tau levels between bvAD and tAD (all p>0.05). Conclusions: Both in-vivo and ex-vivo, patients with bvAD showed heterogeneous distributions of tau pathology. Since key regions involved in behavioural regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.

Details

Authors
  • Ellen Singleton
  • Yolande A.L. Pijnenburg
  • Renaud La Joie
  • William G. Mantyh
  • Evi Berendrecht
  • Bruce L. Miller
  • Leonardo Iaccarino
  • Lauren Edwards
  • Amelia Strom
  • Emma E. Wolters
  • Emma Coomans
  • Denise Visser
  • Sandeep S.V. Golla
  • Hayel Tuncel
  • Femke Bouwman
  • John Cornelis Van Swieten
  • Janne M. Papma
  • Bart Van Berckel
  • Philip Scheltens
  • Anke A. Dijkstra
  • Gil D. Rabinovici
Organisations
External organisations
  • University of California, San Francisco
  • Skåne University Hospital
  • San Raffaele Scientific Institute
  • Erasmus University Medical Center
  • University of Amsterdam
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
JournalJournal of Neurology, Neurosurgery and Psychiatry
Publication statusAccepted/In press - 2021
Publication categoryResearch
Peer-reviewedYes