Summary: Late-life depression and bipolar disorder may be more than psychiatric conditions—they could be early warning signs of neurodegenerative diseases like Alzheimer’s. Using advanced brain imaging and postmortem tissue analysis, researchers found that half of the participants with late-onset mood disorders showed signs of tau accumulation, a key hallmark of neurodegeneration.
Many had abnormal proteins in the brain’s frontal regions years before cognitive symptoms appeared. These findings suggest that tau-PET imaging could help detect dementia in its earliest, non-cognitive stages.
Key Facts:
- Tau Detection: Around 50% of participants with late-life mood disorders showed brain tau buildup.
- Preclinical Symptoms: Mood symptoms preceded cognitive decline by an average of 7.3 years.
- Frontal Lobe Impact: Tau deposits were most prominent in areas tied to emotion and cognition.
Source: QTS
Depression and bipolar disorder of late onset may represent more than just mental health conditions. Growing evidence suggests these late-life mood disorders (LLMDs) could be not merely risk factors, but rather early warning signs of neurodegenerative diseases like dementia, even when they appear years before memory loss or other cognitive symptoms become apparent.
Unfortunately, scientists have struggled to understand the connection between LLMDs and developing dementia at the biological level. While previous research suggested connections between specific disorders like late-life depression and Alzheimer’s disease, the specific neurological mechanisms involved remain mostly unclear.
This knowledge gap is particularly pronounced for late-life bipolar disorder, which has rarely been investigated in relation to dementia.
On top of this, limitations in brain imaging technology have prevented researchers from detecting all the different types of abnormal proteins that might underlie these conditions.
Against this backdrop, a research team led by Dr. Shin Kurose and Dr. Keisuke Takahata from the National Institutes for Quantum Science and Technology (QST), Japan, conducted a comprehensive investigation into the brain changes associated with LLMDs.
Their paper, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association on June 09, 2025, explores the presence of abnormal tau protein—a hallmark of several neurodegenerative diseases—in the brains of people with late-life depression and bipolar disorder. The study was co-authored by Dr. Makoto Higuchi, also from QST, and Dr. Masaki Takao from the National Center of Neurology and Psychiatry.
The researchers used advanced brain imaging techniques to examine 52 participants with LLMDs and 47 healthy controls.
They employed a positron emission tomography (PET) scan using two different tracers, which can detect various forms of tau protein and amyloid beta accumulation, key proteins associated with Alzheimer’s disease, and other neurodegenerative diseases.
To validate their findings, they also analyzed brain tissue samples from 208 autopsy cases, examining the relationship between late-life mood symptoms and the subsequent development of neurodegenerative diseases.
The results were striking: Approximately 50% of participants with LLMDs showed tau accumulation in their brains, compared to only about 15% of healthy controls. Similarly, nearly 29% of participants with LLMDs had detectable amyloid deposits versus just 2% of controls.
The autopsy findings further supported these results, showing a significantly higher prevalence of diverse tau protein-related pathologies in individuals who had experienced late-life mania or depression.
“Because most of the participants with LLMDs in our study had no or mild cognitive decline, these results support the evidence that neurodegenerative diseases, including Alzheimer’s and non-Alzheimer’s tau-related pathologies, can initially manifest as psychiatric symptoms,” highlights Dr. Kurose.
Another noteworthy discovery was that many participants showed tau accumulation in the frontal regions of the brain, which is crucial for emotional regulation and cognitive function.
The study also revealed that these abnormal proteins could be detected years before traditional cognitive symptoms of dementia appeared. As revealed by the autopsy cases, mood symptoms preceded cognitive or motor symptoms by an average of 7.3 years.
“Overall, our findings strongly suggest that tau-PET scans can detect diverse tau pathologies that underlie dementia in patients with LLMDs,” concluded Dr. Takahata.
The insights uncovered in this study have important implications for clinical practice, as some cases of late-life depression and bipolar disorder could likely benefit from an evaluation for underlying neurodegenerative diseases.
Timely identification of these conditions would allow for earlier intervention with disease-modifying treatments. Moreover, the researchers also highlight the value of the tracer molecules used in their PET scans as effective biomarkers for detecting these diverse tau-related pathologies in living patients.
With any luck, these efforts will help solidify our understanding of how neurodegenerative diseases first manifest, leading to earlier diagnosis and potentially better outcomes.
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 represent prodromal manifestations of neurodegenerative dementia; however, the neuropathological basis of LLMDs, including depression and bipolar disorder, remains unclear. We aimed to investigate the involvement of Alzheimer’s disease (AD) and non-AD tau pathologies in LLMD participants.
METHODS
Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent tau and amyloid beta (Aβ) positron emission tomography (PET) imaging using 18F-florzolotau and 11C-Pittsburgh compound B. Additionally, we conducted a clinicopathological correlation analysis in 208 autopsy cases, including various neurodegenerative diseases.
RESULTS
LLMD participants were more likely to be tau PET and Aβ PET positive than HCs. The PET results were supported by the post mortem results that showed a higher likelihood of diverse tauopathies in patients with late-life mania or depression than those without.
DISCUSSION
Our PET and autopsy assays suggest that AD and diverse non-AD tau pathologies might underlie the neuropathological basis of some LLMD cases.
