Involvement of differential tau pathologies in late‐onset bipolar disorder assessed by PET with 18F‐florzolotau

Abstract

AbstractBackgroundNeurodegenerative pathologies, including tau depositions, have been implicated in late‐onset depression (LOD), while there is a lack of in‐vivo evidence for the neuropathological basis of late‐onset bipolar disorder (LOBD) despite postmortem findings of cerebral tau accumulations. The current study aimed to assess tau pathologies in LOBD and LOD patients positron emission tomography (PET) with 18F‐florzolotau, a radioligand for Alzheimer’s disease (AD) and non‐AD tau fibrils.MethodsWe studied LOBD and LOD patients who developed the first episode of mania or depression after age 45. Twenty‐one patients with LOBD (68.8 ± 9.6 years old; 11 females), 15 patients with LOD (73.0 ± 5.8 years old; 11 females), and 39 age‐matched healthy controls (HCs) (67.1 ± 9.1 years old; 19 females) underwent tau and amyloid PET scans with 18F‐florzolotau and 11C‐PiB, respectively. Amyloid positivity was determined by a visual read of 11C‐PiB‐PET images, and tau depositions were assessed by calculating standardized uptake value ratios (SUVRs) in 52 regions covering the cerebral grey matter and basal ganglia to the optimized reference tissue. All SUVRs were corrected for age and sex and converted to Z‐score relative to HCs. The positivity and topology of tau pathologies were determined according to the presence of a region with a Z‐score ≥ 2.0.Results 18F‐florzolotau‐PET positivity was observed in 13 LOBD (62%), 7 LOD (47%), and 11 HC (28%) subjects, whereas 4 LOBD, 4 LOD, and no HC individuals were 11C‐PiB‐PET‐positive. A significant difference in the prevalence of tau pathologies was only found between LOBD and HCs (P = 0.043, corrected for multiple comparisons). Tau topologies in the cases with 11C‐PiB‐PET‐positive AD pathologies consisted of predominant frontal (1 LOBD and 3 LODs), lateral temporal (3 LOBDs and 1 LOD), and posterior (1 LOBD) accumulations. Meanwhile, tau pathologies in 11C‐PiB‐negative cases showed predominant frontal (2 LOBDs and 1 LOD), temporal (1 LOBD and 1 LOD), posterior (4 LOBDs and 1 LOD), and basal ganglia (2 LOBDs) localizations.ConclusionOur findings suggest that a significant subset of LOBD patients harbor tau lesions linked to various AD subtypes and non‐AD tauopathies indicative of distinct early‐stage frontotemporal lobar degeneration subcategories.