Objective: We attempted to reveal the topographical deposition patterns of tau proteins in the living brains of patients with DLB in vivo by virtue of ¹⁸F-Florzolotau PET.

Background: Dementia with Lewy bodies (DLB), as the second most prevalent neurodegenerative dementia, clinically represents progressive cognitive decline like Alzheimer’s disease (AD). [1,2] Regarded as a typical α-synuclein disease, more than 50% DLB cases additionally manifest tau pathology. [3,4] Therefore, the in vivo detection of tau proteins in DLB is urgently needed.

Method: Patients with DLB (n=24), AD (n=43) and cognitively normal controls (n=18) were enrolled and received both clinical assessments and ¹⁸F-Florzolotau PET scans. Additional beta-amyloid (Aβ) detection was acquired in a DLB subgroup (n=5, via CSF; n=7, via ¹⁸F-florbetapir PET). The ¹⁸F-Florzolotau uptake in different brain regions was measured by standard uptake value ratios (SUVRs) and compared via group-wise and voxel-wise analysis.

Results: For ¹⁸F-Florzolotau regional uptake in DLB, prominently elevated signals were detected in widespread cortical regions and putamen. Within DLB group, considering both global and medial temporal lobe (MTL), 17 patients harbored positive ¹⁸F-Florzolotau PET imaging (T+), 13 of whom were also positive in MTL (T_MTL+) and 4 of whom were negative in MTL (T_MTL-), and remaining 7 patients were completely negative (T-T_MTL-). Compared with AD, ¹⁸F-Florzolotau signals in parahippocampal and middle temporal gyrus were significantly lower in DLB, and MTL may assist differential diagnosis between DLB and AD. Furthermore, the ¹⁸F-Florzolotau patterns of those with T_MTL+ were similar to those in AD, while signals in T_MTL– group were notably decreased in specific regions, such as parahippocampal gyrus and precentral gyrus. Moreover, patients with T_MTL+ were accompanied with more severe cognitive impairment compared with those of T_MTL– in DLB. Additionally, patients with amyloid pathology (Aβ) were also common in DLB, accounting for 41.67%.

Conclusion: ¹⁸F-Florzolotau PET uncovered the heterogenous topographical patterns of tau proteins in the living brains of patients with DLB. Promisingly, ¹⁸F-Florzolotau PET may assist the clinically diagnosis and therapeutic explorations in DLB in the coming future.

References: [1] Bousiges, O. & Blanc, F. Biomarkers of Dementia with Lewy Bodies: Differential Diagnostic with Alzheimer’s Disease. Int. J. Mol. Sci. 23, 6371 (2022).
[2] Armstrong, M. J. Advances in dementia with Lewy bodies. Ther. Adv. Neurol. Disord. 14, 17562864211057666 (2021).
[3] Chin, K. S. Prevalence and clinical associations of tau in Lewy body dementias: A systematic review and meta-analysis. (2020).
[4] Gibson, L. L., Abdelnour, C., Chong, J., Ballard, C. & Aarsland, D. Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers. 36, (2023).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/18f-florzolotau-pet-uncovers-the-co-pathological-heterogeneity-of-tau-protein-in-dementia-with-lewy-bodies/