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

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title = "Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease",
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.",
author = "Ellen Singleton and Oskar Hansson and Pijnenburg, {Yolande A.L.} and {La Joie}, Renaud and Mantyh, {William G.} and Pontus Tideman and Erik Stomrud and Antoine Leuzy and Maurits Johansson and Olof Strandberg and Ruben Smith and Evi Berendrecht and Miller, {Bruce L.} and Leonardo Iaccarino and Lauren Edwards and Amelia Strom and Wolters, {Emma E.} and Emma Coomans and Denise Visser and Golla, {Sandeep S.V.} and Hayel Tuncel and Femke Bouwman and {Van Swieten}, {John Cornelis} and Papma, {Janne M.} and {Van Berckel}, Bart and Philip Scheltens and Dijkstra, {Anke A.} and Rabinovici, {Gil D.} and Rik Ossenkoppele",
year = "2021",
doi = "10.1136/jnnp-2020-325497",
language = "English",
journal = "Journal of Neurology, Neurosurgery and Psychiatry",
issn = "1468-330X",
publisher = "BMJ Publishing Group",