The world this wiki

The idea of LLM Wiki applied to a year of the Economist. Have an LLM keep a wiki up-to-date about companies, people & countries while reading through all articles of the economist from Q2 2025 until Q2 2026.

DOsinga/the_world_this_wiki

topics|Mind the gap

Alzheimer's disease

The most common form of dementia. Between 1995 and 2021 private money spent on Alzheimer's research came to $42.5bn, but more than 140 trials failed to yield a single drug capable of slowing the disease. Women are twice as likely to develop Alzheimer's as men, a difference that cannot be explained solely by their longer lifespans. At any given stage of the disease, tau proteins spread farther in women's brains than in men's.

The amyloid hypothesis

For decades the dominant theory has been that the primary cause of Alzheimer's is the accumulation of plaques of beta-amyloid proteins in the brain, leading to neuronal dysfunction, brain-cell death and neuroinflammation. The hypothesis was supported by genetic evidence linking mutations in certain genes to early onset of the disease. James Rowe, a professor of cognitive neurology at the University of Cambridge, argues that although amyloid accumulation is a critical "early trigger", by the time patients present clinically, other processes are accelerating the illness: accumulation of misshapen tau protein, increased metabolic stress on brain cells, neuroinflammation and degeneration of the brain's blood supply.

Drug pipeline

There were 182 clinical trials for Alzheimer's treatments under way in 2025—an 11% increase on the year before—testing 138 different drugs.

Approved drugs. The first two drugs capable of slowing Alzheimer's arrived on the market in quick succession: lecanemab in 2023 and donanemab in 2024. Both help clear amyloid from the brain and slow disease progression by about one-third, meaning patients can retain their quality of life for longer. They offer modest benefits to a subset of patients for whom they are thought to be safe and useful.

Repurposed drugs. Fully one-third of the drugs in the 2025 pipeline are repurposed from other conditions, which allows faster approval and cheaper development because safety profiles are already known. Examples include:

  • Semaglutide, a diabetes and weight-loss drug, is being tested for mild cognitive impairment owing to its anti-inflammatory and metabolic benefits.
  • Piromelatine works on melatonin and serotonin receptors to regulate sleep; healthy sleep is thought to increase clearance of amyloid and other waste proteins.
  • AR1001 (mirodenafil), originally developed for erectile dysfunction, increases levels of a molecule called cGMP that supports nerve-cell survival and may improve the brain's vascular health.
  • Nabilone, which interacts with cannabinoid receptors and was originally developed for chemotherapy-induced nausea, is being tested for agitation and behavioural problems.
  • Guanfacine, used for ADHD, is being tested for its potential to improve attention and executive function.

Novel approaches. Particular attention is being paid to microglia, brain cells that play an important role in the immune response. They have been described as acting as the brain's fire service, police and binmen. A number of drugs are trying to target the protein TREM2 on the surface of microglia to boost their activity. Combination therapies—such as pairing the cancer drug dasatinib with quercetin, a plant-derived molecule, to clear ageing cells—are also being tested, following the model of combination treatments that transformed outcomes in cancer and HIV.

Synthetic proteins. The Institute for Protein Design at the University of Washington, led by David Baker, is using AI-designed proteins that bind to the molecular precursors of the neuronal plaques and tangles found in the brains of those afflicted.

The problem with any unwritten law is that you don't know where to go to erase it. -- Glaser and Way