High prevalence of tau pathologies in late-onset psychosis: A PET study

Late-onset psychosis (LOP) exhibits distinct clinical features compared with younger-onset psychosis. Although postmortem and epidemiological studies have suggested an association between LOP and neurodegenerative processes, particularly tauopathies, in vivo evidence remains limited. This study aimed to investigate the involvement of Alzheimer’s disease (AD) and non-AD tauopathies in LOP using amyloid PET and tau PET with florzolotau (18F) (¹⁸F-florzolotau; also known as ¹⁸F-APN-1607 or ¹⁸F-PM-PBB3), a tracer capable of detecting a broad range of tau pathologies. Thirty-seven patients with LOP and 47 age-matched controls underwent PET scans with ¹¹C-PiB and ¹⁸F-florzolotau to assess group differences in amyloid beta (Aβ) and tau accumulation. Diagnostic effects on regional ¹⁸F-florzolotau standardized uptake value ratios (SUVRs) were assessed. Associations between regional SUVRs and cognitive and clinical features were examined separately in Aβ-positive and Aβ-negative subgroups. Patients exhibited significantly higher positivity rates for both Aβ (13 of 37 patients, 35.1%) and tau (24 patients, 64.9%) than controls (one of 47 controls, 2.1% for Aβ and seven controls, 14.9% for tau). A significant diagnostic effect was observed on regional ¹⁸F-florzolotau SUVRs (P = 0.004), with post-hoc analyses revealing increased tracer retention in the parietal cortex. This diagnostic effect remained robust when the analysis was restricted to Aβ-negative participants (P = 0.002). Among Aβ-positive patients, greater parietal tau burden was associated with lower Frontal Assessment Battery scores. In conclusion, this in vivo PET study demonstrated a high prevalence of AD-like and non-AD-like tau accumulation patterns in LOP, suggesting that LOP may be associated with heterogeneous tau-related neurodegenerative processes.