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[1]. 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[4]. 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[5]. 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[6]. 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: [1] 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. [2] 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. [3] 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. [4] 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). [5] 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). [6] 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. [7] 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. [8] 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.

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/lateralized-tau-pathology-in-a-case-of-lewy-body-dementia-with-corticobasal-syndrome/