Alzheimer's Disease

The most common cause of dementia: Alois Alzheimer's 1906 case, amyloid plaques and tau tangles, symptoms and stages, risk factors, diagnosis with scans and blood tests, and the first drugs that modestly slow it.

Auguste D.

In 1901 the German psychiatrist Alois Alzheimer began caring for Auguste Deter, a 51-year-old woman in Frankfurt with memory loss, confusion and paranoia. "I have lost myself," she told him. After her death in 1906 he examined her brain and described two abnormalities: clumps between neurons (plaques) and twisted fibres inside them (tangles). His colleague Emil Kraepelin named the condition after him.

Plaques and tangles

Plaques are made of amyloid-beta, a protein fragment that accumulates outside neurons. Tangles are made of tau, a protein that normally stabilises the internal skeleton of axons but becomes abnormal and clumps. Amyloid changes begin perhaps 15–20 years before symptoms; tau spreads through the brain in a predictable pattern, starting in the entorhinal cortex and hippocampus, and tracks symptoms closely. Inflammation involving microglia, vascular damage and synapse loss all contribute.

Symptoms

The typical first symptom is difficulty remembering recent events and conversations, while older memories are preserved. Over years, problems spread to language, finding the way, planning, judgement and recognising people, and eventually to basic daily activities. Progression varies, often over 8–10 years or more.

Who gets it

The World Health Organization estimates that more than 55 million people live with dementia worldwide, and Alzheimer's accounts for about 60–70% of cases. Age is the biggest risk factor. The APOE ε4 gene variant raises risk substantially (one copy several-fold, two copies more), and rare mutations cause early-onset familial forms, sometimes in people's forties. The 2024 Lancet Commission estimated that around 45% of dementia might be preventable or delayed by addressing risk factors such as hearing loss, high blood pressure, high LDL cholesterol, smoking, physical inactivity, diabetes and social isolation.

Diagnosis and treatment

Diagnosis combines clinical assessment and cognitive tests with biomarkers: PET scans for amyloid and tau, spinal fluid tests and, increasingly, blood tests measuring forms of tau such as p-tau217; in 2025 the US FDA cleared the first blood test to aid diagnosis. Older drugs such as donepezil modestly ease symptoms. Antibodies that clear amyloid — lecanemab (fully approved in the US in July 2023) and donanemab (approved July 2024) — slowed decline by roughly a quarter to a third over 18 months in early-stage patients in trials. Their benefit is modest, they require regular infusions and monitoring, and they carry a risk of brain swelling and bleeding (ARIA).