What causes Alzheimer's disease?

In 1906, Alois Alzheimer examined the brain of Auguste Deter, a woman who had died at fifty-five after years of profound memory loss, and found it riddled with two kinds of debris: sticky plaques between the neurons and twisted fiber tangles inside them. More than a century later, those plaques and tangles still define the disease, tens of millions of people live with it, and the field still argues about whether Alzheimer saw the cause of the illness or its wreckage.

Why it matters

Alzheimer’s is the most common cause of dementia and one of the leading causes of death in wealthy countries, with care costs measured in the hundreds of billions per year and a burden that falls heavily on families. It is also a scientific test case: the field bet most of its resources for three decades on one hypothesis, and the payoff has been real but strikingly small. Knowing the true causal chain would tell us whom to treat, when, and with what, and whether prevention is possible at all.

What has been tried

The plaques are amyloid-beta; the tangles are tau. The amyloid hypothesis, formalized in 1992, holds that amyloid buildup is the root event that sets tau and neurodegeneration in motion. Its supporting evidence is genuinely strong: rare inherited mutations in amyloid-processing genes guarantee early-onset disease, and people with Down syndrome, who carry an extra copy of the amyloid precursor gene, develop the pathology almost universally. Yet clearing amyloid failed in trial after trial, until recent antibody drugs finally cleared plaques and slowed decline, by roughly a quarter to a third over eighteen months. Slowed, not stopped. Meanwhile rival accounts have matured: tau spreading through the brain tracks symptoms better than amyloid does, and inflammation, vascular injury, metabolic dysfunction, and infections all have serious advocates. The field also absorbed a scandal when images in an influential amyloid paper were found to be manipulated, though the core hypothesis never rested on that work.

Where the edge is

The honest current picture is that amyloid matters and is not the whole story. Some people die with heavy plaque burdens and intact minds. What separates them from patients, how amyloid and tau actually interact, and why age is the overwhelming risk factor all remain open.

What would count as an answer

A causal chain validated by intervention: a treatment aimed at the proposed root cause that largely prevents or halts the disease, not merely slows it, and an account of why some plaque-laden brains never fail.