Researchers at Columbia University have found new evidence to support the “amyloid hypothesis,” but reveal previously unknown details, allowing them to propose a new treatment approach. Article published in the journal Science Advances.
The scientists analyzed the brain cells of people with Alzheimer’s disease and found that their symptoms may indeed be caused by a buildup of beta-amyloid protein clumps in the brain. But the scientists discovered that it wasn’t the amyloids themselves, but rather the “glue” for two other proteins, ATF4 and CREB3L2, in brain neurons.
After pairing CREB3L2-ATF4, a network of other proteins is activated, causing clumps of tau protein to accumulate inside neurons, leading to symptoms of dementia. This protein pair also turns off the cellular machinery that clears neurons of old and damaging proteins, another symptom of Alzheimer’s disease.
The researchers found that although CREB3L2 and ATF4 are found alone in healthy neurons, their interconnection is greatly increased in the presence of excess amyloid.
Scientists have identified the drug dovitinib, which inhibits the formation of the CREB3L2-ATF4 pair. Dovitinib was previously approved by the FDA for the treatment of kidney cancer, but has not been tested for the treatment of Alzheimer’s disease. This means it can be approved for fast track dementia treatment. The scientists added that the drug is not toxic to neurons and penetrates the brain through the blood-brain barrier.