Summary: A new study demonstrates that first-episode hallucinations and delusions appearing after age 40 are frequently driven by underlying neurodegenerative pathology. Using molecular positron emission tomography (PET) imaging, the team discovered that approximately 65% of late-onset psychosis patients exhibit abnormal tau protein accumulation, compared to 15% of healthy older controls, while 35% showed amyloid beta positivity compared to just 2% of controls.
The study provides the first direct in vivo evidence in the living human brain that late-life psychiatric symptoms can stem from distinct neurodegenerative pathways.
Key Facts
- High Prevalence of Tau Pathology: Approximately 65% of patients developing psychosis after age 40 displayed tau PET positivity, more than four times the rate observed in healthy age-matched controls (15%).
- Elevated Amyloid Beta Positivity: 35% of late-onset psychosis patients were amyloid PET positive, compared to only 2% of healthy older controls.
- Two Distinct Pathological Subtypes: PET scans differentiated patients into an Alzheimer’s-type pattern (amyloid-positive with typical tau dissemination) and a non-Alzheimer’s-type pattern (amyloid-negative with localized tau accumulation).
- Posterior Brain Tau Localization: In amyloid-negative patients, tau buildup concentrated in posterior brain regions, specifically the parietal and occipital lobes, areas critical for visual processing, attention, and higher-order spatial cognition.
- Executive Dysfunction Correlation: Higher parietal lobe tau burden in amyloid-positive patients directly correlated with declines in executive function, including planning and attentional control.
Source: QST
Hallucinations and delusions that appear for the first time in midlife or later are often treated as psychiatric symptoms whose biological cause is unclear.
The study, published online in Molecular Psychiatry on August 2, 2026, suggests that, for many patients, these symptoms may be linked to brain changes also seen in dementia.
Using positron emission tomography, or PET, the research team found that about 65% of patients who developed psychosis after age 40 showed abnormal buildup of tau, a protein associated with Alzheimer’s disease and other forms of dementia. By comparison, tau PET positivity was seen in about 15% of healthy older controls. The study also found amyloid PET positivity in 35% of patients, compared with 2% of controls.
The findings provide the first in vivo evidence that diverse tau-related brain changes may be involved in late-onset psychosis. Until now, earlier epidemiological and postmortem studies had suggested a possible relationship between late-life psychotic symptoms and neurodegeneration, but direct evidence in the living brain had been limited.
“Patients can show the same symptoms, such as hallucinations or delusions, but their clinical course and response to treatment can be very different,” said Manabu Kubota, the study’s representative researcher. “This study started from a clinical question: whether hidden biological differences in the brain could explain those differences.”
Late-onset psychosis can place a heavy burden on patients, families and caregivers, especially in aging societies. People who first experience hallucinations or delusions in midlife or later may not always receive medical care, and their symptoms can be difficult to diagnose and manage using psychiatric evaluation alone.
To look for biological signs of disease, the team examined 37 patients with psychosis that began after age 40 and 47 healthy older adults. They used amyloid PET and QST’s tau PET tracer florzolotau (18F), which can visualize a broad range of tau pathologies in the living brain.
The PET scans revealed not only a higher rate of tau positivity among patients, but also diverse patterns of tau buildup. Some patients showed amyloid-positive patterns consistent with Alzheimer’s disease, while others showed amyloid-negative patterns, suggesting non-Alzheimer’s disease types of tau-related neurodegeneration.
In amyloid-negative patients, tau accumulation was especially notable in posterior brain regions, including the parietal and occipital lobes. The researchers suggest that tau buildup in these regions may affect higher cognitive functions such as attention, judgment and problem solving, potentially contributing to psychotic symptoms.
The study also linked tau buildup with cognitive function. Among amyloid-positive patients, greater tau accumulation in the parietal lobe was associated with lower executive function, which includes abilities such as planning and controlling attention. This suggests that the amount of tau in the brain may help explain some clinical features seen in late-onset psychosis.
Alzheimer’s disease diagnosis and treatment increasingly rely on detecting amyloid and tau in the brain. By contrast, objective biological tools for hallucinations and delusions have remained limited. The new findings may help move late-onset psychosis toward earlier diagnosis and intervention based on measurable brain changes rather than symptoms alone.
In the longer term, the researchers hope that PET-based assessment could support more personalized treatment. If doctors can identify whether a patient’s symptoms are related to Alzheimer’s-type or non-Alzheimer’s-type tau pathology, future therapies may be selected or developed according to the patient’s underlying disease process.
Key Questions Answered:
A: Psychotic symptoms appearing for the first time in midlife or later have traditionally been classified as psychiatric disorders with unclear biological causes. Because standard psychiatric evaluations rely on self-reported symptoms rather than objective biological markers, underlying neurodegenerative processes like tau and amyloid buildup are frequently missed, leading to variable treatment responses.
A: Florzolotau (18F) is a specialized radiotracer used in positron emission tomography (PET) scans that binds to and visualizes a wide range of tau protein aggregations in the living brain. It allowed researchers to map tau accumulation in vivo across both Alzheimer’s and non-Alzheimer’s neurodegenerative patterns.
A: The parietal and occipital lobes govern higher cognitive functions, including visual processing, spatial awareness, attention, and sensory integration. When tau protein accumulates in these posterior brain regions, it disrupts neural circuits responsible for processing reality, directly contributing to visual hallucinations, visual-spatial distortions, and impaired judgment.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this psychosis and neurology research news
Author: Rin Suzuki
Source: QST
Contact: Rin Suzuki – QST
Image: The image is credited to Neuroscience News
Original Research: Open access.
“High prevalence of tau pathologies in late-onset psychosis: A PET study” by Manabu Kubota, Shin Kurose, Kenji Tagai, Yuki Momota, Masanori Ichihashi, Hironobu Endo, Chie Seki, Sho Moriguchi, Yasuharu Yamamoto, Yuko Kataoka, Ryoji Goto, Takehiro Tamura, Hiroki Shiwaku, Kiwamu Matsuoka, Hisaomi Suzuki, Mitsumoto Onaya, Takahiko Tokuda, Hiroyuki Uchida, Hidehiko Takahashi, Kazunori Kawamura, Ming-Rong Zhang, Makoto Higuchi & Keisuke Takahata. Molecular Psychiatry
DOI:10.1038/s41380-026-03749-3
Abstract
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.
