A new wave of scientific research is shedding light on how brain changes commonly associated with Alzheimer’s disease may also play a role in mood disorders that appear later in life. Scientists in Japan have discovered unusually high levels of tau and amyloid-beta proteins in older adults diagnosed with long-standing depression and mood disorders — even in those without signs of cognitive decline.
The study, conducted by researchers at Keio University and published in a peer-reviewed neurology journal, involved PET brain scans of 52 individuals aged 40 and above with late-life mood disorders (LLMD), including major depressive disorder and bipolar disorder. Their results were then compared with 47 healthy individuals.
The findings were striking:
- Half of those with LLMD showed abnormal tau buildup, compared to just 15% of healthy peers.
- Nearly 30% had elevated amyloid-beta, a protein often seen in Alzheimer’s patients — yet only 2% of controls showed similar patterns.
Even after ruling out memory loss or dementia, researchers found LLMD patients were significantly more likely to show these abnormal protein deposits. The presence of these biomarkers raises new questions about the biological roots of late-life psychiatric conditions.
Mood Disorders as Early Warning Signs?
“What we’re seeing may be more than just depression,” said Dr. Hiroshi Yamada, one of the study’s lead neurologists. “These protein accumulations suggest a possible link between mood symptoms and the earliest stages of neurodegeneration.”
Autopsy-confirmed data also backed the scan results. Brain tissue from more than 200 deceased patients revealed that individuals who had suffered from depression or bipolar disorder often had Alzheimer’s-type tau or other tau variants, especially in areas of the brain responsible for regulating mood — such as the frontal lobe and limbic system.
One of the more revealing insights: in many cases, patients experienced mood symptoms years before any memory issues, sometimes by more than seven years. This timeline hints that psychiatric symptoms in older adults could be among the first signs of neurological decline.
A Divided Scientific Landscape
Despite the compelling results, the science isn’t settled. Other research groups have reported minimal or no connection between mood disorders and elevated tau or amyloid levels — particularly in patients with depression but no cognitive impairment. Still, the current study stands out due to its focus on a wide range of mood disorders, detailed imaging, and post-mortem validation.
What’s especially noteworthy is the role of tau over amyloid-beta. “Amyloid seems to be less reliable as an indicator in mood disorders,” Dr. Yamada explained. “But tau — especially in emotion-regulating brain regions — could be a key player in understanding why some older adults develop severe, unexplained depression.”
What This Means for the Future
The findings could change how doctors approach mental health in the elderly. If tau buildup is proven to contribute to mood disturbances, therapies targeting tau — already in development for Alzheimer’s — might be repurposed for use in psychiatric care. It could also lead to earlier screenings, using PET scans, for those showing late-onset depression.
“We need to think beyond the idea that mood disorders are purely psychological,” Dr. Yamada said. “In older adults, these symptoms may be tied to subtle, progressive changes in the brain.”
Conclusion
As the global population ages, understanding the overlap between mental illness and neurodegeneration becomes more critical. While more research is needed, studies like this point to a future where treating depression in older adults might also mean intervening in the earliest stages of dementia.
