An interactive journey through the human genome to understand why amyloid and tau build up in the brain — and what role the APOE gene plays.
The whole journey of this page, summed up in steps.
Before getting into the genetics, it helps to understand the disease these genes help explain.
Alzheimer's disease is the most common cause of dementia: a neurodegenerative disease in which the brain accumulates amyloid-β plaques and tau tangles, becomes inflamed and loses neurons, above all in the hippocampus and the cortex. The most typical early symptom is episodic memory loss. The vast majority are late-onset cases driven by genes (especially APOE), age and lifestyle.
In 1906, the physician Alois Alzheimer presented the case of Auguste Deter, a woman with early-onset dementia in whose brain he observed under the microscope the plaques and tangles that define the disease today. Decades later, amyloid, tau and the genes that modulate risk were identified — the starting point for the rest of this page.
The disease progresses in stages and affects several domains, which vary from one person to another:
Forgetting recent facts and conversations, repeating questions and becoming disoriented in time. It reflects the early damage to the hippocampus.
Difficulty planning, solving problems, finding words and orienting in space, as it spreads to the cortex.
Apathy, anxiety, depression, irritability and, in advanced stages, agitation, sleep disturbances or delusions.
Appears from age 65 onward. It does not follow simple inheritance: it depends on many common risk genes (especially APOE), age and lifestyle.
Before age 65, sometimes in the forties. Caused by autosomal dominant mutations in APP, PSEN1 or PSEN2: each child has a 50% risk of inheriting them.
With three copies of chromosome 21 there is an extra dose of the APP gene: amyloid pathology is almost universal and Alzheimer's appears at early ages.
Brain changes begin years before the first symptoms. Clinical progression is usually described in stages:
Brain changes are already present (amyloid, tau), but the person has no symptoms. Detectable only through biomarkers.
Noticeable memory lapses that do not yet interfere with daily life. Not everyone progresses to dementia.
Forgetfulness that affects everyday life, difficulties with words and orientation. This is usually when diagnosis happens.
Greater dependence: confusion, behavioral changes and the need for help with everyday tasks.
Loss of communication and autonomy; total dependence and continuous care.
There is no treatment that cures the disease, but there are drugs and supports that improve symptoms and, for the first time, therapies that act on its biology:
Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine: improve or stabilize symptoms for a time, without slowing the cause.
Lecanemab and donanemab clear amyloid and modestly slow decline in early stages. They require monitoring for adverse effects (ARIA).
Cognitive stimulation, adapting the environment, managing vascular factors and, above all, support for caregivers: cornerstones of management.
Educational content with a scientific basis (Alzheimer 1906; the amyloid hypothesis; the GWAS of Bellenguez et al. 2022; lecanemab, van Dyck et al. 2023). It does not replace assessment by a healthcare professional.
DNA (deoxyribonucleic acid) is the molecule that stores the genetic instructions of every living thing, spread across about 3 billion base pairs.
Four bases — A, T, C and G — form the double helix. In Alzheimer's, certain variants alter how the brain produces and clears amyloid and how its immune system responds, raising the risk of neurodegeneration.
Alzheimer's genes are scattered across the whole genome. Click a chromosome to see its regions, the evidence and the genes involved.
Causal and risk genes of Alzheimer's disease. Search and filter by cellular mechanism; click a card to see its function and the studies.
Alzheimer's genes converge on just a few brain processes. Hover over a node to identify the gene; click to see the detail.
From the first case described by Alois Alzheimer to the 75 risk loci and the anti-amyloid antibodies.
How Alzheimer's genes drive amyloid plaques, tau tangles and the brain's immune response.
Alzheimer's is highly heritable — twin studies estimate around 70% — but only a small fraction follows simple familial inheritance.
Fewer than 5% are early-onset forms caused by mutations in APP, PSEN1 or PSEN2. In late-onset Alzheimer's (the vast majority), the most powerful common genetic factor is the APOE ε4 allele, which can multiply the risk several times over.
The essentials about the genetics of Alzheimer's disease:
The key point: inheriting the APOE ε4 allele raises the risk, but it is not a sentence. Genetics guides prevention and, today, guides the first anti-amyloid therapies.
Alzheimer's does not damage the brain evenly: it begins in the memory regions and spreads to the rest of the cortex. Click a region to see its role.
The APOE gene has three variants (ε2, ε3, ε4) and you inherit one from each parent. Choose a combination to see how the relative risk changes compared with ε3/ε3 (the most common reference).
Indicative figures (based on Corder et al. 1993 and later meta-analyses; they vary with population, sex and age). APOE ε4 is a risk factor, not destiny: many people with ε4 never develop Alzheimer's, and many without ε4 do.
It helps to separate science from myths and distinguish modifiable risk from false causes:
An isolated lapse is not Alzheimer's, and aging does not mean you will develop it. There is a real modifiable risk: managing blood pressure, diabetes and hearing, exercising, not smoking and staying physically, mentally and socially active reduces the risk, though it does not eliminate it.
After a century of hypotheses, genetics and biomarkers are transforming how Alzheimer's is detected and treated.
In 2023, lecanemab showed for the first time a clear clinical benefit by clearing amyloid, confirming its causal role. Donanemab followed soon after: the era of disease-modifiers has begun, though with modest effects.
Blood tests such as p-tau217 can detect Alzheimer's pathology without a lumbar puncture or PET, opening the door to an early and accessible diagnosis.
Polygenic risk scores together with the APOE genotype are beginning to guide whom and when to treat or enroll in prevention trials.
Because tau correlates better with symptoms, halting its aggregation and spread is one of the major goals of the next generation of drugs.
Acting on TREM2 and other immune targets to help the brain clear amyloid and tau without harming neurons.
With biomarkers and genetics, treating in the preclinical phase — before decline appears — could be the most effective strategy.
Research is moving fast and some of these results are recent: dates and specific figures may change as the trials mature.
The questions that come up most when learning about the genetics of Alzheimer's.
Milestones and scientific sources this page is based on.
An educational synthesis page; it is not a primary clinical source. For medical decisions, consult professionals and the official resources on Alzheimer's.
Six questions to check what you take away. It grades itself: tap an answer and you'll instantly see whether you're right, with the explanation.