Objective: To compare the regional distribution of cortical tau pathology between Lewy body disorders (LBD: Parkinson’s disease and dementia with Lewy bodies (DLB)) and progressive supranuclear palsy (PSP) using digital histologic measurements in grey and white matter (GM and WM).

Background: Alpha-synuclein is the primary pathology in LBD; however, half of LBD patients have moderate to severe Alzheimer’s disease (AD) at autopsy, which is associated with decreased survival and faster time to dementia. Tau is the primary pathology in PSP, but there are few studies of the distribution of tau in PSP, and no direct comparisons to clinically similar LBD.

Method: 10 neuropathological cases of PSP with focal cognitive deficits (5: primary progressive aphasia, 5 behavioral variant FTD) and 20 cases of LBD with Medium/high AD neuropathologic change were selected (LBD+AD: 12 DLB and 8 PDD). Sections from angular gyrus (ANG), superior temporal gyrus (STC), and mid-frontal gyrus (MFC) were stained for tau (AT8).Lamina slide scanning system and Halo digital image software v1.90 calculated percentage area occupied (%AO) of tau in GM and WM. %AO was natural log-transformed (ln) to obtain normal distribution. T-tests compared regional GM and WM tau between LBD+AD and PSP and within LBD+AD and PSP.

Results: LBD+AD and PSP had equivalent GM tau%AO (LBD+AD ln tau%AO mean(SD):-0.58(1.84) PSP:-1.21(1.5), p=0.4). STC had the highest GM tau%AO in LBD+AD (STC: 0.38(2.24) ANG:-0.73(1.90), MFC:-1.40(1.98). p<0.001 for both) which was also higher than PSP (PSP STC:-1.82(1.99), p=0.02). ANG had the highest GM tau%AO (ANG:-1.17(1.89)), but not significantly greater than STC or MFC (p>0.05). WM tau burden was higher in PSP than LBD+AD (LBD+AD:-1.63(1.59) PSP:-3.00(1.12). p=0.01). WM burden was highest in STC in LBD+AD (STC:-2.25(1.38) ANG:-3.15(1.38), MFC: -3.59(1.22), p<0.001 for each) which was equivalent to PSP, but all other regions had higher WM tau%AO in PSP (MFC:-1.65(1.61) p<0.01 ANG:-1.86(1.41), p=0.03).

Conclusion: In this pilot study comparing tau pathology between LBD+AD and PSP using digital histology, we found selectively greater GM tau burden in LBD+AD than PSP in the STC. WM tau pathology was more severe in PSP than LBD+AD in all other regions.  Further studies will elucidate the consequences of these distinct regional patters of tau pathology for disease progression, survival and in vivo clinical manifestations of disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparative-grey-and-white-matter-tau-pathology-in-lbd-and-psp-using-digital-histologic-measurements/