Summary: Late-onset depression and bipolar disorder may be early indicators of neurodegenerative disease rather than solely psychiatric conditions. Using advanced tau and amyloid PET imaging alongside postmortem tissue analyses, researchers identified tau accumulation in roughly half of people with late-life mood disorders, often concentrated in frontal brain regions years before cognitive decline became evident.
These results indicate that tau-PET imaging and targeted biomarker assessment could detect dementia-related pathology during a preclinical window when symptoms are primarily mood-related, improving opportunities for earlier diagnosis and intervention.
Key Facts:
- Tau detection: About 50% of participants with late-life mood disorders (LLMDs) showed measurable brain tau accumulation.
- Preclinical interval: Mood symptoms often appeared well before cognitive decline—on average 7.3 years before cognitive or motor symptoms in autopsy cases.
- Frontal lobe involvement: Tau deposits were frequently located in frontal regions linked to emotion regulation and executive function.
Source: QTS
Late-onset depression and bipolar disorder can be more than isolated psychiatric illnesses. Increasing evidence shows that these late-life mood disorders (LLMDs) may signal underlying neurodegenerative processes, including Alzheimer’s disease (AD) and non-AD tauopathies, even when cognitive deficits are not yet apparent.
Until now, clarifying the biological link between LLMDs and later dementia has been challenging. Prior studies connected late-life depression to Alzheimer’s risk, but the precise neuropathological mechanisms—especially for late-onset bipolar disorder—remained underexplored. Limited imaging tools also complicated efforts to detect multiple tau variants and other abnormal proteins in living patients.
To address these gaps, a team led by Dr. Shin Kurose and Dr. Keisuke Takahata at the National Institutes for Quantum Science and Technology (QST), Japan, together with colleagues including Dr. Makoto Higuchi (QST) and Dr. Masaki Takao (National Center of Neurology and Psychiatry), conducted a multimodal study examining tau and amyloid pathologies in LLMD.
Published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association on June 9, 2025, the study combined in vivo PET imaging with a clinicopathological analysis of autopsy samples to evaluate whether Alzheimer’s disease and diverse non-AD tau pathologies underlie some cases of late-life depression and bipolar disorder.
The imaging cohort included 52 participants with LLMD and 47 age- and sex-matched healthy controls. Researchers used two PET tracers—18F-florzolotau for tau detection and 11C-Pittsburgh compound B for amyloid beta—to identify abnormal protein deposition patterns. To corroborate imaging findings, they reviewed 208 autopsy cases covering a range of neurodegenerative disorders and correlated prior mood symptoms with pathologic diagnoses.
Findings were notable: nearly half of LLMD participants were tau-PET positive, while only about 15% of controls showed comparable tau signals. Amyloid positivity was also higher among LLMD participants (approximately 29%) versus controls (around 2%). Autopsy analyses mirrored imaging results, revealing a higher prevalence of diverse tauopathies in individuals who had experienced late-life mania or depression compared with those without late-life mood symptoms.
A clear pattern emerged: tau pathology in LLMD frequently involved frontal brain regions critical to emotion and cognition. Because most study participants had none or only mild cognitive impairment at the time of imaging, these data strengthen the hypothesis that neurodegenerative pathologies—both AD and non-AD tau-related disorders—can first present as psychiatric symptoms, sometimes many years prior to classic dementia signs.
Autopsy case reviews provided additional temporal perspective: mood symptoms preceded the onset of cognitive or motor manifestations by an average of 7.3 years, highlighting a substantial preclinical period during which biomarker-based screening might identify at-risk individuals.
“Overall, our results indicate that tau-PET is capable of detecting a range of tau pathologies in patients presenting with late-life mood disorders,” said Dr. Takahata. The investigators emphasize that the PET tracers used in the study perform well as in vivo biomarkers for diverse tau-related pathologies.
Clinical implications are significant: when older adults present with new-onset depression or bipolar symptoms, clinicians should consider the possibility of an underlying neurodegenerative process. Early detection through targeted imaging and biomarker assessment can open the door to disease-modifying treatments and more informed care planning.
These findings contribute to a growing understanding of how dementia can first manifest through mood and behavioral changes. By identifying tau and amyloid pathology during this preclinical phase, researchers and clinicians may improve early diagnosis, monitor progression more effectively, and ultimately enhance treatment strategies for people at risk of Alzheimer’s and related tauopathies.
About this mental health and Alzheimer’s disease research news
Author: International Affairs and Public Relations Section
Source: QTS
Contact: International Affairs and Public Relations Section – QTS
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Diverse tau pathologies in late-life mood disorders revealed by PET and autopsy assays” by Shin Kurose et al. Alzheimer’s & Dementia
Abstract
Diverse tau pathologies in late-life mood disorders revealed by PET and autopsy assays
INTRODUCTION
Late-life mood disorders (LLMDs) may in some cases represent prodromal stages of neurodegenerative dementia. The precise neuropathological basis underlying late-onset depression and bipolar disorder is not fully understood. This study investigates the contribution of Alzheimer’s disease and non-Alzheimer’s tau pathologies in individuals with LLMD.
METHODS
Fifty-two participants with LLMD and 47 age- and sex-matched healthy controls underwent PET imaging for tau and amyloid beta using 18F-florzolotau and 11C-Pittsburgh compound B. Additionally, a clinicopathological correlation was performed in 208 autopsy cases encompassing a spectrum of neurodegenerative disorders.
RESULTS
Participants with LLMD were more likely to test positive on tau and amyloid PET scans than healthy controls. Postmortem analyses supported these imaging results, demonstrating a higher incidence of diverse tauopathies among individuals who had experienced late-life mania or depression.
DISCUSSION
Combined PET and autopsy findings suggest that Alzheimer’s disease and a variety of non-AD tau pathologies may underlie the neuropathological basis of some cases of late-life mood disorders, underscoring the importance of biomarker-driven assessment in older adults with new-onset psychiatric symptoms.