Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading form of dementia. It accounts for around 60–70% of dementia cases. The condition was named after the physician Alois Alzheimer, who first described it in 1906. Its symptoms usually begin after age 65, although a small number of inherited cases start much earlier. Its underlying causes are only partly understood, and no treatment has yet stopped the disease, although some drugs can slow its progression in the early stages.
Clinical features
Memory loss is the defining early symptom. The most common early symptom is difficulty in remembering recent events. Patients may also find it hard to concentrate, to handle several tasks at once, or to manage finances. Alzheimer's disease causes trouble concentrating and thinking, especially about abstract concepts such as numbers. Early on, the person may notice these problems themselves, while family members often recognize them more clearly as the disease advances.
Clinicians commonly describe the course in stages. In the mild stage, people can still live independently but have trouble with everyday tasks such as managing money. As the disease progresses, disorientation, changes in mood and behavior, and suspicion of others increase, and difficulty speaking, swallowing and walking may emerge. People in the later stages of the disease usually can't live alone or care for themselves. Because the disease changes over several years, the sequence of symptoms varies between individuals.
Pathology
Alzheimer's disease is defined by two abnormal structures in the brain. The first is extracellular amyloid plaques, which are deposits of amyloid-β peptide, a fragment cleaved from the amyloid precursor protein (see amyloid-β). The second is intracellular neurofibrillary tangles, which consist of the microtubule-associated protein tau in an abnormally aggregated form. The affected brain exhibits astroglyosis, nerve cell atrophy and neuronal loss, alongside these deposits.
Neuronal loss is the process that links these deposits to symptoms. It's the destruction and death of nerve cells that causes memory failure, personality changes, problems carrying out daily activities and other symptoms of Alzheimer's disease. The loss also disrupts communication between regions of the brain and between nerve cells, so the neurons that remain cannot transmit information properly. In advanced disease, the brain visibly shrinks as tissue is lost.
The pathological changes begin long before symptoms. Brain changes in Alzheimer's begin a decade or more before symptoms appear. Plaques and tangles can accumulate silently during this preclinical phase, which is why research increasingly focuses on early intervention.
Causes and risk factors
Alzheimer's disease is usually divided into two forms. Familial (early-onset) cases are rare and caused by inherited mutations. The 'amyloid-first' view has strong empirical support in familial AD, where gene mutations (APP, PSEN1, PSEN2) associated with abnormal Aβ peptide production have been shown to cause autosomal dominant forms of the disease. Sporadic (late-onset) cases make up the great majority of patients. Sporadic AD is believed to be caused by a complex combination of genetic and environmental factors.
Among the most important genetic risk factors is a variant of the APOE gene, which affects how the brain handles lipids and amyloid. Other recognized risk factors include genetics, head injuries, clinical depression, hypertension, psychological stress, lack of physical and mental exercise. Many of these, such as hypertension and physical inactivity, are modifiable, which is why public health strategies emphasize vascular health and activity across the lifespan.
Diagnosis
Diagnosis is clinical and based on the history of symptoms, cognitive testing, and the exclusion of other causes. Differential diagnosis includes normal brain aging, Lewy body dementia, and Trisomy 21, among other conditions. Specialized tests can now support the diagnosis. Blood tests can measure levels of proteins linked to Alzheimer's, and a spinal tap may be ordered if needed. Doctors may also perform brain scans to support an Alzheimer's diagnosis or to rule out other possible causes of symptoms. Such biomarkers are important because they can detect pathology before symptoms appear.
Scientific hypotheses
The dominant explanation for the disease has been the amyloid hypothesis, which holds that amyloid-β accumulation initiates the pathological cascade. A majority of researchers support the alternative hypothesis that amyloid is the primary causative agent. However, the hypothesis faces significant challenges. All attempts to develop Aβ-targeting drugs to treat AD have ended in failure in the trials reviewed by one 2018 article, and the correlation between plaque burden and cognitive decline is weak.
An alternative view emphasizes tau. The poor correlation between Aβ plaques and neurodegeneration/cognitive impairment, the spaciotemporal disparity between Aβ and tau pathology, and the disappointing results following several large clinical trials using Aβ-targeting agents have been cited as reasons to doubt the amyloid-first model. Proponents of the tau hypothesis argue that tau is the main driver of progression, but this claim is also contested. Some researchers propose that the two pathologies begin as independent processes; one 2023 analysis suggested that widespread neocortical tau results from the local interaction of amyloid-β and tau. Other proposals include vascular disturbance, chronic inflammation, and metabolic dysfunction. The field is therefore best described as one in which multiple mechanisms are considered, with no single cause yet firmly established.
Treatment
No treatment is known to cure Alzheimer's disease. Symptomatic drugs, such as cholinesterase inhibitors and the NMDA receptor antagonist memantine, can temporarily improve cognition or daily functioning in some patients, though their effect is modest. The more significant recent development is the class of disease-modifying antibodies. Two treatments designed to clear toxic amyloid-beta from the brain were approved by the FDA: Leqembi (lecanemab) and Kisunla (donanemab). Lecanemab (Leqembi) is an antibody intravenous (IV) infusion therapy that targets and removes beta-amyloid from the brain. These agents are monoclonal antibodies that bind amyloid and promote its clearance, and they are sometimes called anti-amyloid therapies.
Clinical trials show that these drugs reduce amyloid levels, but their effect on cognition is smaller and their benefits are limited to the early stages. In phase II and phase III trials, donanemab and lecanemab showed significant reductions in amyloid plaque compared to placebo. Their use is restricted to people with mild cognitive impairment or mild dementia. Their main safety concern is amyloid-related imaging abnormalities (ARIA), which although frequently asymptomatic, can be serious and require monitoring.
Regulatory and access decisions vary by country. Lecanemab received approval from the European Commission in April 2026. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) has repeatedly declined to recommend the drugs for NHS use, citing cost; the cost of implementing donanemab and lecanemab across the NHS was "substantially higher" than considered acceptable for taxpayers' money and NHS resources. Dosing is also changing: in July 2026 the FDA approved a subcutaneous starter dose of lecanemab, which allows the full course to be given under the skin.
Other approaches are under investigation. Ongoing clinical trials are working to bring better treatments to market, including therapies targeting amyloid as well as tau, the other protein implicated in Alzheimer disease. Trials are also testing treatment before symptoms begin; the AHEAD study, for example, evaluates the effectiveness of early treatment with Leqembi in people at high risk for Alzheimer's but before symptoms begin.
Epidemiology
Alzheimer's disease is a major public health concern because of its prevalence and the growing number of older adults. About 6.9 million people in the United States age 65 and older live with Alzheimer's disease. Globally, of the more than 55 million people in the world with dementia, 60% to 70% are estimated to have Alzheimer's disease. Because age is the strongest known risk factor, prevalence is expected to rise as populations age. The subject is studied within epidemiology and medicine.
Research and controversies
Research now targets earlier stages, biomarkers, and combination approaches. We can now detect changes in the brain before symptoms ever appear, and that gives us a therapeutic window. Debates continue over whether amyloid is a cause or a consequence of disease, why trials have repeatedly failed, how to weigh the modest benefits of current drugs against their cost and risks, and how to define a disease whose pathology begins decades before diagnosis. Research into the role of inflammation and the immune system in the brain is also expanding, reflecting the view that the disease may involve more than protein deposition alone.
References
- Alzheimer's diseaseen.wikipedia.org
- Alzheimer's disease - Symptoms and causes - Mayo Clinicmayoclinic.org
- What is Alzheimer's Disease? Symptoms & Causesalz.org
- Alzheimer's Disease Symptoms: A Complete Guidewebmd.com
- Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Diseasencbi.nlm.nih.gov
- Alzheimer's Diseasehealth.nih.gov
- Tau-first subtype of Alzheimer’s disease consistently identified across in vivo and post mortem studiesbiorxiv.org
- Biochemistry of Alzheimer's diseaseen.wikipedia.org
- Primary age-related tauopathy and the amyloid cascade hypothesis: the exception that proves the rule?ncbi.nlm.nih.gov
- data-driven study of Alzheimer's disease related amyloid and tau pathology progressionacademic.oup.com
- Expanding the Alzheimer’s Treatment Landscape: A 2026 Forecastbrightfocus.org
- Lecanemab Approved for Treatment of Early Alzheimer’salz.org
- Donanemab and lecanemab in Alzheimer's disease treatment: A narrative review of clinical trials and discussion of implications for patient access - ScienceDirectsciencedirect.com
- AAN 2026: Early Detection Changes Everything in Alzheimer Disease Care—And Pharmacists Are Uniquely Positioned to Helppharmacytimes.com
- NICE opens consultation on previously-rejected Alzheimer’s treatments donanemab and lecanemab - The Pharmaceutical Journalpharmaceutical-journal.com
- Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease - PMCpmc.ncbi.nlm.nih.gov