RT Journal Article
SR Electronic
T1 Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer’s disease
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 872
OP 880
DO 10.1136/jnnp-2020-325497
VO 92
IS 8
A1 Ellen Singleton
A1 Oskar Hansson
A1 Yolande A. L. Pijnenburg
A1 Renaud La Joie
A1 William G Mantyh
A1 Pontus Tideman
A1 Erik Stomrud
A1 Antoine Leuzy
A1 Maurits Johansson
A1 Olof Strandberg
A1 Ruben Smith
A1 Evi Berendrecht
A1 Bruce L Miller
A1 Leonardo Iaccarino
A1 Lauren Edwards
A1 Amelia Strom
A1 Emma E Wolters
A1 Emma Coomans
A1 Denise Visser
A1 Sandeep S V Golla
A1 Hayel Tuncel
A1 Femke Bouwman
A1 John Cornelis Van Swieten
A1 Janne M Papma
A1 Bart van Berckel
A1 Philip Scheltens
A1 Anke A. Dijkstra
A1 Gil D Rabinovici
A1 Rik Ossenkoppele
YR 2021
UL http://jnnp.bmj.com/content/92/8/872.abstract
AB 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.Data are available upon reasonable request. Anonymised data used in the present study may be available upon reasonable request to the corresponding author.