For decades, Alzheimer’s research has centered on two suspects: amyloid beta plaques and tau tangles. But a 2025 study out of Harvard Medical School has put a new, unexpected player in the spotlight — lithium, the same element long used to treat bipolar disorder, but here found in trace amounts as a naturally occurring part of a healthy brain.
Lithium Isn’t Just a Drug — It’s a Nutrient
Most people know lithium only as a psychiatric medication, prescribed at relatively high doses. But the Harvard team, led by geneticist and neurologist Bruce Yankner, found that lithium exists naturally in the brain at much lower, biologically meaningful levels — and that it plays an essential role in normal brain function.
Their decade-long study combined mouse experiments with analyses of human brain and blood tissue across the full spectrum of cognitive health, from normal aging to mild cognitive impairment to full Alzheimer’s.
An Early Warning Sign
One of the study’s central findings: loss of lithium in the human brain is among the earliest changes associated with the onset of Alzheimer’s disease — showing up before the more familiar hallmarks of the disease take hold. In fact, lithium was the only metal that differed significantly between people with and without mild cognitive impairment, a condition that often precedes Alzheimer’s.
The Plaque Trap
So where does the lithium go? The researchers found the answer lies with amyloid beta itself. As amyloid beta starts forming plaques in the earliest stages of dementia, it binds to lithium, effectively trapping it and reducing its availability elsewhere in the brain. The lithium isn’t gone from the brain entirely — it’s just locked away, unable to do its job.
This creates a kind of vicious cycle: the very protein deposits that define Alzheimer’s disease appear to disable a nutrient the brain needs to defend itself against those same deposits.
The consequences of this lithium depletion aren’t limited to one type of brain cell. The drop in bioavailable lithium affects neurons, astrocytes, microglia, and other major brain cell types, and in mouse models, produces changes that closely mirror Alzheimer’s disease — including memory loss, increased plaque burden, and impaired function of the cells responsible for clearing cellular debris.
From Correlation to Cause
Human brain tissue analysis can only show association. To test causation, the researchers put mice on lithium-deficient diets. Those mice developed worse pathology — more amyloid plaques, impaired learning and memory, and disrupted function in neurons and the microglia that normally help clear amyloid debris. Simply removing lithium from the diet, Yankner noted, had wide-ranging effects on brain cell biology, Alzheimer’s pathology, and cognitive function.
Not All Lithium Is Equal
If lithium deficiency contributes to Alzheimer’s, could restoring it help? The catch is that standard lithium compounds — including lithium carbonate, the form used in psychiatric medicine — tend to get trapped by amyloid plaques in the same way the brain’s own natural lithium does.
To get around this, the researchers screened for lithium compounds that could evade capture by amyloid beta. They landed on lithium orotate as the most promising candidate. In mouse studies, treatment with lithium orotate:
• Reversed learning and memory impairments
• Reduced beta-amyloid plaque burden by around 70% in aging mice
• In some mice with advanced disease, nearly eliminated amyloid beta plaques altogether
• Protected mice from developing Alzheimer’s-like symptoms in the first place, when given from early adulthood
Why This Matters
Most Alzheimer’s drug development has focused narrowly on removing amyloid plaques or tau tangles — with mixed results. Yankner has suggested that lithium’s role may open the door to treating the disease more broadly, rather than targeting a single feature of it.
It’s also a compelling explanation for a long-standing puzzle: why two people with similar genetic risk and similar amyloid buildup can have very different outcomes. Lithium availability may be part of that missing piece.
The Caveats
This is genuinely exciting science, but it’s worth staying grounded:
• It’s one study, however rigorous. Replication by independent research groups will matter before this becomes established science.
• The treatment results are in mice, not people. There’s no human trial data yet showing that lithium orotate supplementation prevents or treats Alzheimer’s.
• Lithium has real risks. At higher (psychiatric) doses, lithium carbonate has a narrow therapeutic window and can affect the kidneys and thyroid. Over-the-counter lithium orotate supplements aren’t regulated the way prescription lithium is, and self-supplementing without medical guidance isn’t something this research supports.
For now, the takeaway isn’t “start taking lithium supplements” — it’s that a decades-old, unassuming trace mineral may turn out to be a key thread connecting the biology of Alzheimer’s disease, and that thread is now being actively pulled on by researchers around the world.
Source: Based on research published in Nature by Aron et al., “Lithium deficiency and the onset of Alzheimer’s disease,” Harvard Medical School, 2025.
