Brain Health Basics
Over 60 million people worldwide are living with Alzheimer's. Here is what the disease actually does to the brain — and why it has proven so difficult to treat.
Alzheimer's disease is the most prevalent neurodegenerative disorder in the world, accounting for 60–70% of all dementia cases. Despite its scale, it remains widely misunderstood — often described simply as a memory condition, when in reality it is a progressive disease of the entire brain, with a biology that begins unfolding years, sometimes decades, before any symptoms appear.
60M+
people worldwide are currently living with Alzheimer's disease
~20 years
biological changes can precede clinical symptoms by up to two decades
>50%
of cases are linked to the APOE4 genetic variant
Dementia is not a single disease. It is an umbrella term for a set of symptoms that include memory loss, difficulties with reasoning and language, and changes in behaviour. Alzheimer's disease is the most common cause of dementia, but other causes include vascular dementia (caused by impaired blood flow to the brain), Lewy body dementia, and frontotemporal dementia. Each has a distinct underlying biology, although there is considerable overlap in symptoms, and mixed dementias — where more than one type is present — are common in older patients.
Understanding this distinction matters, because it shapes how we think about treatment. A drug or intervention that targets the biology of Alzheimer's specifically will not necessarily help someone whose dementia has a different cause. This is part of why Alzheimer's research focuses so closely on the molecular mechanisms unique to the disease.
Alzheimer's disease is defined by the abnormal accumulation of two proteins in the brain: amyloid-beta and tau.
Amyloid-beta is a small protein fragment produced naturally during normal brain activity. In healthy brains, it is cleared efficiently. In Alzheimer's, this clearance system fails, and amyloid-beta begins to clump together into insoluble deposits known as plaques, which accumulate in the spaces between neurons. The plaques themselves are toxic, triggering an inflammatory response that damages surrounding cells.
Tau is a protein that normally helps stabilise the internal scaffolding of neurons. In Alzheimer's, tau becomes chemically altered and begins to aggregate into neurofibrillary tangles inside neurons. These tangles disrupt the neuron's ability to transport nutrients and signals internally, eventually killing the cell.
The energy connection
Both amyloid plaques and tau tangles impair the function of mitochondria — the structures within neurons responsible for producing energy. This energy failure is increasingly understood as a central driver of neuronal death in Alzheimer's, not merely a downstream consequence of it. It is this link that underpins OneCarbon's research into metabolic support for neurons.
A third hallmark of the disease is neuroinflammation. The brain's immune cells, called microglia, are activated by the presence of plaques and tangles and mount an inflammatory response. While this is initially a protective attempt to clear the damage, chronic neuroinflammation ultimately contributes to further neuronal injury — a self-reinforcing cycle that accelerates disease progression.
Alzheimer's follows a broadly predictable trajectory, though the pace varies considerably between individuals. Crucially, the biology of the disease begins long before any clinical symptoms emerge.
Stage 1 — Preclinical
Amyloid begins to accumulate. No symptoms. Can last 15–20 years. Detectable only via brain imaging or cerebrospinal fluid analysis.
Stage 2 — Mild Cognitive Impairment
Subtle memory lapses or processing difficulties. Daily function largely intact. Not all MCI progresses to Alzheimer's.
Stage 3 — Mild Dementia
Memory loss becomes noticeable. Difficulties with complex tasks, language, and navigation begin to emerge.
Stage 4 — Moderate to Severe
Significant cognitive and functional decline. Increasing dependence on care. Loss of recognition of people and places.
The biological changes of Alzheimer's disease precede clinical symptoms by up to two decades — the most important window for preventive intervention.
Age is the single largest risk factor for Alzheimer's disease. The prevalence roughly doubles every five years after age 65, affecting approximately one in fourteen people in that age group, rising to one in six by age 80. However, age is not a cause — it is a proxy for the cumulative biological changes that increase vulnerability over time.
Genetics play a significant role. The APOE4 variant is the most important genetic risk factor for late-onset Alzheimer's, and is estimated to account for over 50% of all cases. Carrying one copy of the variant approximately triples the lifetime risk; carrying two copies increases it by up to tenfold. Importantly, APOE4 is not a deterministic gene. Many carriers never develop the disease, but it substantially shifts the probability, and it appears to interact with the metabolic vulnerabilities that our research targets.
A smaller proportion of cases — around 1–2% — are caused by rare inherited mutations that virtually guarantee early-onset Alzheimer's, sometimes in people in their 40s or 50s. These familial forms of the disease have been scientifically valuable precisely because they are so predictable, allowing researchers to study the disease's biology well in advance of symptom onset.
Modifiable lifestyle factors also influence risk. Cardiovascular health is closely linked to brain health — conditions such as hypertension, type 2 diabetes, and obesity in midlife are all associated with elevated Alzheimer's risk, likely through their effects on cerebral blood flow and neuronal metabolism. Physical inactivity, social isolation, poor sleep, and low levels of cognitive engagement have also been identified as risk factors in large epidemiological studies, suggesting that a meaningful proportion of cases may be attributable to preventable causes.
Despite decades of research and billions of dollars invested, Alzheimer's disease has proven extraordinarily resistant to treatment. The history of drug development in this area is one of the highest failure rates in all of medicine — over 99% of clinical trials have failed to produce meaningful benefit.
Several factors explain this. First, by the time symptoms are apparent and treatment begins, substantial and irreversible neuronal loss has already occurred — the therapeutic window has partly closed. Second, the biology of Alzheimer's is complex and multi-factorial; targeting amyloid alone, for example, has proven insufficient even when the protein is successfully cleared. Third, the brain is extraordinarily difficult to access pharmacologically, protected by the blood-brain barrier that limits which molecules can enter.
Two drugs — lecanemab and donanemab — have recently received regulatory approval for early Alzheimer's, and do appear to slow cognitive decline modestly by clearing amyloid. But both carry significant risks of brain swelling and bleeding, require intravenous infusion, and are prohibitively expensive for most health systems. They represent progress, but not a solution.
OneCarbon's research takes a fundamentally different approach to this problem. Rather than targeting the downstream pathology of Alzheimer's after it has formed, our work focuses on strengthening the metabolic resilience of neurons during the long preclinical window that precedes neuronal loss.
Our AI-driven analysis of multiomics data identified one-carbon metabolism — a key cellular energy pathway — as a critical mechanism by which neurons protect themselves under the conditions of Alzheimer's disease. By supporting this pathway through our probiotic 1C-01, we aim to give neurons the metabolic resources they need to maintain function for longer. We are still gathering the clinical evidence, and 1C-01 has not been proven to prevent or treat Alzheimer's disease. But the biological rationale is grounded in robust preclinical and human genetic data — and the earlier the intervention, the greater the potential benefit.