Alzheimer’s Disease: What We Know, What We Don’t, and What Is Emerging
Alzheimer’s disease is often introduced as a disorder of memory. Clinically, it is more consequential than that. It is a progressive neurodegenerative disease that can impair learning, language, executive function, judgment, behavior, and eventually the capacity to live independently. The underlying biological changes can develop years before a person meets the clinical criteria for dementia.
Its population impact is substantial. The Alzheimer’s Association estimates that 7.4 million Americans age 65 and older are living with Alzheimer’s disease in 2026, approximately one in nine people in that age group. Nearly 13 million Americans provide unpaid care for someone living with Alzheimer’s or another dementia. The effects of this disease therefore extend well beyond the individual diagnosis.
At the Institute for Human Optimization, we approach long-term health through a framework often referred to as the Four Horsemen: cardiovascular disease, cancer, metabolic dysfunction, and neurodegenerative disease. These are not isolated silos. They are overlapping categories of risk, linked through biological processes that include vascular injury, inflammation, altered nutrient signaling, mitochondrial dysfunction, and impaired cellular repair.
Alzheimer’s sits within the neurodegenerative category, but its biology also intersects with cardiovascular and metabolic health. That overlap shapes our philosophy: prevent the preventable, reverse the reversible, and delay the inevitable. It does not mean that every disease can be prevented or reversed. It means identifying which risks can be modified, which contributors to symptoms can be treated, and where emerging research may eventually change the course of disease.
What is Alzheimer’s disease?
Alzheimer’s disease is the most common cause of dementia. Dementia describes a clinical syndrome in which cognitive impairment interferes with everyday functioning; Alzheimer’s disease refers to a particular underlying disease process. A person can have Alzheimer’s-related brain changes before developing dementia, and not every person with dementia has Alzheimer’s.
Two central features of Alzheimer’s pathology are extracellular amyloid-beta plaques and intracellular aggregates of abnormal tau protein. These occur alongside synaptic dysfunction, loss of neurons, and changes in brain networks involved in memory and cognition. Research increasingly examines these changes as part of a wider system involving neuroinflammation, vascular function, energy metabolism, and the brain’s response to injury.
A cognitive complaint should never be reduced to a single biomarker or presumed diagnosis. Sleep disorders, medication effects, depression, thyroid disease, nutritional deficiencies, and other conditions may contribute to impaired thinking. Some can be treated. A careful evaluation helps distinguish those contributors from an underlying neurodegenerative disease and recognizes that both may be present at the same time.
Genetics informs risk, but rarely determines an individual outcome
The APOE ε4 variant is the best-known genetic risk factor for the more common, later-onset form of Alzheimer’s. APOE participates in lipid transport and has been studied in relation to amyloid handling, inflammation, and vascular biology. Carrying ε4 increases risk but does not make disease inevitable; people without it can also develop Alzheimer’s.
Much rarer inherited variants in APP, PSEN1, and PSEN2 can cause autosomal dominant Alzheimer’s disease, often with earlier onset and a recognizable pattern across generations. When that family history is suspected, genetic counseling is an important part of deciding whether and how to test.
Genetics offers biological insight, but a risk variant is not equivalent to a diagnosis. It must be interpreted alongside symptoms, family history, examination, and appropriate testing.
Why do some researchers call Alzheimer’s “type 3 diabetes”?
The phrase “type 3 diabetes” arose from research into impaired insulin signaling and glucose metabolism in the brain. Insulin has roles in neuronal signaling, synaptic function, and cellular metabolism that extend beyond its familiar role in regulating blood sugar. Investigators have examined whether disruptions in these pathways contribute to amyloid accumulation, abnormal tau processing, inflammation, and cognitive decline.
The hypothesis is supported by several converging observations. Type 2 diabetes and metabolic dysfunction are associated with greater dementia risk. Studies have identified altered insulin signaling in Alzheimer’s-affected brain tissue, while brain imaging has long documented reduced glucose utilization in characteristic regions of the brain. Researchers are also examining interactions among insulin-related signaling, mitochondrial function, oxidative stress, and inflammatory pathways.
That makes “type 3 diabetes” a useful mechanistic lens: it asks whether disturbed energy regulation is a contributor to neurodegeneration rather than merely a coincidental finding. It does not require us to reduce Alzheimer’s to one pathway. Amyloid, tau, vascular disease, genetics, and metabolic dysfunction may influence one another, and their relative importance may differ between patients or stages of disease.
The clinical implication is to take metabolic health seriously without claiming that correcting insulin resistance alone has been proven to prevent or reverse Alzheimer’s disease. The distinction between a compelling mechanism and a demonstrated patient benefit remains essential.
Diagnosis and treatment are advancing
Alzheimer’s evaluation is becoming more biologically precise. Clinical history and cognitive assessment remain foundational, while amyloid imaging, cerebrospinal-fluid markers, and blood-based tests can provide additional information in the right setting. In 2025, the FDA cleared a blood test to aid diagnosis in symptomatic adults evaluated in specialized care. It is not intended as stand-alone diagnosis or broad screening of people without symptoms.
Treatment has also entered a new phase. In randomized trials, the anti-amyloid therapies lecanemab and donanemab modestly slowed clinical decline in selected patients with early symptomatic Alzheimer’s disease. That is meaningful progress, not a cure. Treatment requires careful assessment of potential benefit, eligibility, and adverse effects including amyloid-related imaging abnormalities that may involve brain swelling or bleeding.
These advances reinforce the importance of identifying the disease accurately and understanding which stage of disease and which patient population a study actually examined.
What remains unresolved?
We still cannot fully explain why Alzheimer’s begins in one person and not another, why its progression varies, or how its biological pathways interact over time. We do not know whether targeting one mechanism will be sufficient for most patients, or whether future care will require combinations tailored to disease biology and stage.
We also must distinguish biomarker changes from clinical outcomes. A treatment that changes amyloid, inflammation, or a measure of biological age has not necessarily shown that it preserves memory, function, or independence. Those outcomes require rigorous studies in people.
What is emerging?
Research is investigating approaches beyond amyloid, including tau-directed strategies, metabolic and vascular pathways, neuroinflammation, and methods of identifying disease earlier. These are areas of active study, not interchangeable treatment options with established benefits.
Therapeutic plasma exchange (TPE) is one such investigational area. In the AMBAR trial, 347 people with mild-to-moderate Alzheimer’s disease were assigned to a sham procedure or a prolonged regimen of plasma exchange with albumin replacement. At approximately 14 months, the combined treatment groups had less decline in activities of daily living. A co-primary measure of cognition favored treatment but did not meet the conventional threshold for statistical significance in the overall population. Findings also varied by disease severity.
AMBAR warrants further investigation, but it does not establish TPE as a standard Alzheimer’s treatment or show that a small number of sessions would produce the same outcome. TPE is an invasive medical procedure, and any consideration of it requires an individualized assessment of evidence, alternatives, and risks.
The Institute for Human Optimization participates in clinical research related to Alzheimer’s disease because progress depends on disciplined investigation. Research participation has its own oversight, eligibility requirements, and informed-consent process. It is separate from clinical care and from any individualized consideration of TPE.
A rigorous form of optimism
The field is moving forward. We understand more about Alzheimer’s pathology, genetics, and the potential contribution of metabolic dysfunction. We can investigate disease biology more precisely, and some patients now have treatments that modestly slow decline. At the same time, important mechanisms remain unresolved and no intervention can honestly be promised to prevent or reverse Alzheimer’s for an individual.
Our approach is to connect these lines of evidence without collapsing the distinction between risk, mechanism, diagnosis, and demonstrated treatment benefit. For patients and families, that means taking cognitive changes seriously, investigating what may be treatable, and making decisions grounded in both scientific possibility and clinical reality.
If you or someone you care for is experiencing cognitive changes, begin with an individualized medical evaluation. To learn about the Institute’s approach to brain health or inquire about research opportunities, contact our team. An inquiry does not establish eligibility for a clinical trial or suitability for any procedure.
This article is educational and does not replace individualized medical advice. Therapeutic plasma exchange is not an established treatment to prevent, reverse, or cure Alzheimer’s disease. Clinical research and clinical services require separate evaluation and informed consent.
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