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

Singleton, Ellen ; Hansson, Oskar LU ; Pijnenburg, Yolande A.L. ; La Joie, Renaud ; Mantyh, William G. ; Tideman, Pontus LU ; Stomrud, Erik LU ; Leuzy, Antoine LU ; Johansson, Maurits LU and Strandberg, Olof LU , et al. (2021) In Journal of Neurology, Neurosurgery and Psychiatry
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... (More)

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.

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Contribution to journal
publication status
in press
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in
Journal of Neurology, Neurosurgery and Psychiatry
publisher
BMJ Publishing Group
external identifiers
  • scopus:85104490625
  • pmid:33850001
ISSN
0022-3050
DOI
10.1136/jnnp-2020-325497
language
English
LU publication?
yes
id
4c6c99c8-08de-4f67-8495-25b0b98088f4
date added to LUP
2021-05-03 14:38:32
date last changed
2021-06-16 02:32:54
@article{4c6c99c8-08de-4f67-8495-25b0b98088f4,
  abstract     = {<p>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&lt;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&gt;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.</p>},
  author       = {Singleton, Ellen and Hansson, Oskar and Pijnenburg, Yolande A.L. and La Joie, Renaud and Mantyh, William G. and Tideman, Pontus and Stomrud, Erik and Leuzy, Antoine and Johansson, Maurits and Strandberg, Olof and Smith, Ruben and Berendrecht, Evi and Miller, Bruce L. and Iaccarino, Leonardo and Edwards, Lauren and Strom, Amelia and Wolters, Emma E. and Coomans, Emma and Visser, Denise and Golla, Sandeep S.V. and Tuncel, Hayel and Bouwman, Femke and Van Swieten, John Cornelis and Papma, Janne M. and Van Berckel, Bart and Scheltens, Philip and Dijkstra, Anke A. and Rabinovici, Gil D. and Ossenkoppele, Rik},
  issn         = {0022-3050},
  language     = {eng},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Neurology, Neurosurgery and Psychiatry},
  title        = {Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease},
  url          = {http://dx.doi.org/10.1136/jnnp-2020-325497},
  doi          = {10.1136/jnnp-2020-325497},
  year         = {2021},
}