TY - JOUR
T1 - Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease
AU - Singleton, Ellen
AU - Hansson, Oskar
AU - Pijnenburg, Yolande A. L.
AU - la Joie, Renaud
AU - Mantyh, William G.
AU - Tideman, Pontus
AU - Stomrud, Erik
AU - Leuzy, Antoine
AU - Johansson, Maurits
AU - Strandberg, Olof
AU - Smith, Ruben
AU - Berendrecht, Evi
AU - Miller, Bruce L.
AU - Iaccarino, Leonardo
AU - Edwards, Lauren
AU - Strom, Amelia
AU - Wolters, Emma E.
AU - Coomans, Emma
AU - Visser, Denise
AU - Golla, Sandeep S. V.
AU - Tuncel, Hayel
AU - Bouwman, Femke
AU - van Swieten, John Cornelis
AU - Papma, Janne M.
AU - van Berckel, Bart
AU - Scheltens, Philip
AU - Dijkstra, Anke A.
AU - Rabinovici, Gil D.
AU - Ossenkoppele, Rik
N1 - Funding Information:
Funding Work at the Alzheimer Center Amsterdam was supported by the Netherlands Organization for Health Research and Development, ZonMw (70- 73305-98-1214 to Rik Ossenkoppele, PI). Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research programme of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. Work at the University of California San Francisco was supported by the NIH National Institute on Aging (NIA) grants R01-AG045611 (to GDR) and the Robert W. Katzman Fellowship Training Grant through the American Academy of Neurology in conjunction with the American Brain Foundation and Alzheimer’s Association (A133766) to (to WGM), as well as funding for Aging and Dementia Research Center (NIA P30-AG062422) and PPG (NIA P01-AG019724). Work at the Skåne University Hospital and Lund University was supported by the Swedish Research Council, the Knut and Alice Wallenberg foundation, the Marianne and Marcus Wallenberg foundation, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Skåne University Hospital Foundation and the Swedish federal government under the ALF agreement.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85104490625&partnerID=8YFLogxK
U2 - 10.1136/jnnp-2020-325497
DO - 10.1136/jnnp-2020-325497
M3 - Article
C2 - 33850001
VL - 92
SP - 872
EP - 880
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
SN - 0022-3050
IS - 8
ER -