Category: Parkinsonism, Others
Objective: To measure bilateral in vivo and postmortem tau pathology in a well-characterized patient presenting with corticobasal syndrome (CBS) due to underlying neocortical stage Lewy body disease (LBD) with Alzheimer’s disease (AD) co-pathology.
Background: Tau co-pathology is a common postmortem finding, correlating with specific cognitive features and poor outcomes in LBD. CBS is characterized by lateralized frontoparietal symptoms due to a variety of neuropathologies[2,3]. Detailed interhemispheric examination of postmortem pathology is rarely studied in CBS despite lateralized symptoms.
Method: Flortaucipir PET scanning was obtained 8 months prior to death using published protocols and parcellated into 116 brain regions. Postmortem brain tissue was sampled from 17 bilateral regions and immunostained for tau (AT8), amyloid-β (NAB228), and aSyn (MJF R-13). % area occupied (%AO) of immunostain was derived for each region using validated digital methods. Asymmetry indices ((L-R)/(L+R)*100) for average SUVR in frontal, temporal, parietal and occipital cortices and %AO of regional pathologies were calculated and compared to a hypothesized mean of 0 (i.e. symmetric disease) using one-sided t-tests.
Results: The patient presented with left-lateralized neglect, myoclonus and visuospatial and executive impairments, consistent with a diagnosis of CBS. Later in the course, well-formed visual hallucinations and parkinsonism emerged fulfilling clinical criteria for dementia with Lewy bodies. Average cortical flortaucipir SUVR was 1.51 (Left hemisphere SUVR=1.40±0.27. Right hemisphere SUVR=1.61± 0.36) with significant right lateralization in all lobes (t=4.3-10.1, all p<0.01). Neuropathological examination found neocortical stage LBD and high level ADNPC[7,8]. There was significant right lateralization of tau and aSyn pathology (Tau: right%AO=42.3%±21.3, left%AO=30.0%± 24.0 t=3.0, p=0.008. aSYN right%AO=28.4%±23.7, left%AO=19.4%±24.7 t=2.6, p=0.02). Amyloid-β pathology was not lateralized (p=0.8).
Conclusion: In this unique analysis of laterality of pathology in a patient presenting with symptoms of right-hemispheric disease, we found evidence of antemortem right-lateralized tau pathology by flortaucipir PET scan, confirmed postmortem with digital measures of tau and aSyn pathology. This novel data suggests a synergistic interaction between tau and aSyn and supports a strong clinical influence of tau pathology in LBD.
References:  D.G. Coughlin, H.I. Hurtig, D.J. Irwin, Pathological Influences on Clinical Heterogeneity in Lewy Body Diseases, Mov. Disord. (2019). https://doi.org/10.1002/mds.27867.  K. Kasanuki, K.A. Josephs, T.J. Ferman, M.E. Murray, S. Koga, T. Konno, N. Sakae, A. Parks, R.J. Uitti, J.A. Van Gerpen, N.R. Graff-Radford, Z.K. Wszolek, D.W. Dickson, Diffuse Lewy body disease manifesting as corticobasal syndrome A rare form of Lewy body disease, Neurology. 91 (2018) E268–E279. https://doi.org/10.1212/WNL.0000000000005828.  M.J. Armstrong, I. Litvan, A.E. Lang, T.H. Bak, K.P. Bhatia, B. Borroni, A.L. Boxer, D.W. Dickson, M. Grossman, M. Hallett, K.A. Josephs, A. Kertesz, S.E. Lee, B.L. Miller, S.G. Reich, D.E. Riley, E. Tolosa, A.I. Troster, M. Vidailhet, W.J. Weiner, Criteria for the diagnosis of corticobasal degeneration, Neurology. 80 (2013) 496–503. https://doi.org/10.1212/WNL.0b013e31827f0fd1.  D.G. Coughlin, J.S. Phillips, E. Roll, C. Peterson, R. Lobrovich, K. Rascovsky, M. Ungrady, D.A. Wolk, S. Das, D. Weintraub, Multimodal In Vivo and Post-mortem Assessments of Tau in Lewy Body Disorders, Neurobiol. Aging. (2020).  D.G. Coughlin, R. Ittyerah, C. Peterson, J.S. Phillips, S. Miller, K. Rascovsky, D. Weintraub, A.D. Siderowf, J.E. Duda, H.I. Hurtig, Hippocampal subfield pathologic burden in Lewy body diseases vs. Alzheimer’s disease, Neuropathol. Appl. Neurobiol. (2020).  I.G. McKeith, B.F. Boeve, D.W. Dickson, G. Halliday, J.-P. Taylor, D. Weintraub, D. Aarsland, J. Galvin, J. Attems, C.G. Ballard, Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium, Neurology. 89 (2017) 88–100.  I.G. McKeith, D.W. Dickson, J. Lowe, M. Emre, J.T. O’Brien, H. Feldman, J. Cummings, J.E. Duda, C. Lippa, E.K. Perry, D. Aarsland, H. Arai, C.G. Ballard, B. Boeve, D.J. Burn, D. Costa, T. Del Ser, B. Dubois, D. Galasko, S. Gauthier, C.G. Goetz, E. Gomez-Tortosa, G. Halliday, L.A. Hansen, J. Hardy, T. Iwatsubo, R.N. Kalaria, D. Kaufer, R.A. Kenny, A. Korczyn, K. Kosaka, V.M. Lee, A. Lees, I. Litvan, E. Londos, O.L. Lopez, S. Minoshima, Y. Mizuno, J.A. Molina, E.B. Mukaetova-Ladinska, F. Pasquier, R.H. Perry, J.B. Schulz, J.Q. Trojanowski, M. Yamada, Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium, Neurology. 65 (2005) 1863–1872. https://doi.org/10.1212/01.wnl.0000187889.17253.b1.  T.J. Montine, C.H. Phelps, T.G. Beach, E.H. Bigio, N.J. Cairns, D.W. Dickson, C. Duyckaerts, M.P. Frosch, E. Masliah, S.S. Mirra, P.T. Nelson, J.A. Schneider, D.R. Thal, J.Q. Trojanowski, H. V Vinters, B.T. Hyman, National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach, Acta Neuropathol. 123 (2012) 1–11. https://doi.org/10.1007/s00401-011-0910-3.
To cite this abstract in AMA style:D. Coughlin, H. Coslett, C. Mcmillan, J. Phillips, E. Lee, J. Trojanowski, M. Grossman, D. Irwin. Lateralized Tau Pathology in a Case of Lewy Body Dementia with Corticobasal Syndrome [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/lateralized-tau-pathology-in-a-case-of-lewy-body-dementia-with-corticobasal-syndrome/. Accessed December 7, 2023.
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