Summary: Depression and bipolar disorder in old age may be more than just psychological conditions: They may be early signs of neurodegenerative diseases like Alzheimer’s. Using advanced brain imaging and post-mortem tissue analysis, researchers found that half of participants with late-onset mood disorders showed signs of tau protein accumulation, a key marker of neurodegeneration.
In many patients, the abnormal protein was present in the frontal regions of the brain for many years before the first cognitive symptoms. These results suggest that tau PET scans may help detect dementia in the early, non-cognitive stages.
Important facts:
- Detecting Tao: In about 50% of participants who suffered from mood disorders in older age, tau accumulation was observed in the brain.
- Preclinical symptoms: Mood complaints preceded cognitive decline by an average of 7.3 years.
- Effect on the frontal lobe: Tau levels were higher in areas related to emotion and cognition.
Source: QTS
Depression and bipolar disorder that develop later in life may signal more than just psychiatric concerns. Increasing research suggests these late‑life mood disorders could serve not only as risk factors, but also as early warning signs of neurodegenerative conditions such as dementia sometimes appearing many years before memory loss or other cognitive changes become noticeable.
Unfortunately, scientists have struggled to understand the biological link between LLMD and the development of dementia. While previous research suggests links between specific conditions, such as late-onset depression and Alzheimer’s disease, the specific neural mechanisms involved are largely unknown. This cognitive gap is particularly important in the case of late-onset bipolar disorder, which has rarely been studied in relation to dementia.
Furthermore, limitations in brain imaging technology prevent researchers from being able to detect all the different types of abnormal proteins that can cause these diseases. Building on that, the study by Dr. Shin Kurose, Dr. Keisuke Takahata, and colleagues at Japan’s National Institute of Quantum Science and Technology (QST) was one of the most detailed investigations to date into the biological underpinnings of late‑life mood disorders (LLMDs).
Published on June 9, 2025 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study investigates the presence of abnormal tau protein a key hallmark of several neurodegenerative diseases in the brains of individuals with late‑life depression and bipolar disorder. The research was co‑authored by Dr. Makoto Higuchi of QST and Dr. Masaaki Takao of the National Center for Neurology and Psychiatry.
The researchers used advanced brain imaging techniques to examine 52 participants with LLMD and 47 healthy controls. They used positron emission tomography (PET) scans with two different tracers, which can detect different forms of tau and beta-amyloid protein accumulations. These are key proteins associated with Alzheimer’s disease and other neurodegenerative diseases.
They examined the relationship between mood swings in older adults and the later development of neurodegenerative diseases.
The results were striking: Nearly 50% of participants with LLMD had tau protein deposits in their brains, compared to only 15% of healthy controls. Nearly 29% of participants with LLMD had detectable amyloid deposits, compared to only 2% of controls. Autopsy results confirmed these findings, showing a significantly higher prevalence of multiple tau-related pathologies in individuals who experienced manic or depressive episodes in later life.
“Given that most participants with LLMD in our study had no cognitive impairment, these findings support the evidence that neurodegenerative diseases, including Alzheimer’s and non-Alzheimer’s disease, can present with early psychiatric symptoms.”
Another notable finding is that many participants showed accumulation of tau in the frontal regions of the brain, which is important for regulating emotions and cognitive functions. The study also found that these abnormal proteins could be detected many years before the onset of traditional cognitive symptoms of dementia.
“Overall, our results strongly suggest that tau positron emission tomography (PET) scans can detect various tau pathologies underlying dementia in patients with LLMD,” concluded Dr. Takahata.
The results of this study have important implications for clinical practice, as some cases of depression and bipolar disorder in later life may benefit from investigation of underlying neurodegenerative diseases.
Early identification of these pathologies would enable early intervention with disease-modifying therapies. Furthermore, the researchers emphasize the value of the tracer molecules used in their PET studies as effective biomarkers for detecting these various tau-related pathologies in living patients. We hope that these efforts will increase our understanding of how neurodegenerative diseases manifest early, leading to earlier diagnosis and potentially better outcomes.
Abstract
Multiple tau pathologies revealed in late-life mood disorders by PET and postmortem tests
Introduction
Late-onset mood disorders (LOMDs) may be prodromal manifestations of neurodegenerative dementia. We aimed to investigate the involvement of Alzheimer’s disease (AD) and non-AD tau pathologies in participants with LOMD.
Methods
Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent positron emission tomography (PET) imaging of tau and amyloid beta (Aβ) proteins using 18F-florzolotau and 11C-Pittsburgh Compound B. Postmortem cases, including various neurodegenerative diseases.
Results
LLMD participants were more likely to have positive tau-PET and Aβ-PET results than MS patients. These findings were confirmed by postmortem observations, which showed that patients with mania or depression were more likely to develop various tauopathies in later life than those without them.
Discussion
Our PET and autopsy studies suggest that AD and multiple non-AD tau pathologies may underlie some cases of LLMD.
