Alzheimer's Drugs Are Finally Tackling the Disease Itself. Here's How

"Alzheimer's disease has proved to be a tricky target, and researchers and drug developers have been pursuing effective treatments for decades. Debates rage over the disorder's underlying causes, and various approaches have faced one hurdle after another. But the field has reached a turning point. Over the past four years the U.S. Food and Drug Administration has approved several therapies that address some of the condition's potential biological roots rather than merely mitigating symptoms-a key scientific milestone."

"The brains of people who die with Alzheimer's show a distinct biology: clumps or "plaques" of amyloid beta proteins in spaces between neurons and tangles of tau proteins that accumulate primarily within the nerve cells. One prevailing theory holds that amyloid builds up early, and tau tangles develop when nerve cell damage is underway but cognitive symptoms are not yet apparent."

Brains of people who die with Alzheimer's show amyloid-beta plaques between neurons and tau tangles inside nerve cells. Amyloid buildup often begins decades before cognitive symptoms, and tau tangles appear once nerve cell damage is underway. Lecanemab and donanemab bind to amyloid-beta, clear it from the brain, and modestly slow cognitive decline. Amyloid and tau also accumulate in other neurodegenerative disorders, and progression from protein pathology to dementia is variable. There can be a 20- to 30-year lag between initial amyloid detection and obvious cognitive decline. Fewer than one quarter of cognitively healthy 75-year-old women who test positive for amyloid will develop Alzheimer's dementia during their lifetime, indicating that amyloid alone does not fully drive disease progression and that many questions remain.

Read at Nature