Alzheimer’s disease is the most common form of dementia, affecting millions worldwide. The prevailing hypothesis blames toxic amyloid aggregates, specifically the Abeta42 protein, for damaging brain cells. However, researchers from the Karolinska Institute (ki.se) and the University of Cincinnati challenge this idea.
Their studies reveal that reducing these aggregates in clinical trials has not improved symptoms—sometimes making them worse. Moreover, amyloid accumulation is common in aging, yet most people with amyloid deposits never develop dementia. By age 85, 60% of individuals have amyloids, but only 10% suffer from dementia.
The scientists propose a different explanation: Alzheimer’s may be caused by the loss of Abeta42’s function rather than the toxicity of its aggregates. When this soluble protein clumps together, it becomes insoluble and non-functional, disrupting critical brain processes. Their research on nearly 600 individuals shows that those with higher levels of soluble Abeta42 maintain cognitive function and have a normal-sized hippocampus – a key brain region for memory.
This breakthrough shifts the focus from removing amyloids to restoring functional Abeta42 proteins. The team is now developing therapeutics using non-aggregating protein analogs to help prevent and treat Alzheimer’s and other neurodegenerative diseases.
