Dennis Selkoe, MD: Current Challenges in Alzheimer Disease and Hope for the Future

“We’re going to be having blood tests, very soon I think, within a year, that you can measure in spinal fluid.”

At the 2018 Alzheimer’s Association International Conference held in Chicago, Illinois, Dennis Selkoe, MD, Coates Professor of Neurologic Diseases at Harvard Medical School and co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Health Center, sat down with NeurologyLive to discuss many topics in the Alzheimer space.

Selkoe first discussed results from an exploratory analysis of the phase II BLAZE and ABBY clinical trials which studied the impact of crenezumab treatment on beta amyloid oligomer levels in cerebrospinal fluid (CSF) in subjects with mild to moderate Alzheimer disease. He noted that this is the first time anyone has shown direct evidence of target engagement of toxic forms of amyloid in humans. The results, Selkoe added, strongly suggest target engagement and recommends assaying CSF Aβ oligomers in upcoming trials.

Next, Selkoe spoke to his excitement in field, and that after much debate and controversy surrounding the amyloid hypothesis theory, there now comes evidence it actually works. Evidence presented at the meeting demonstrated that after treating subjects for 18 months with the antibody BAN2401, cognitive decline was slowed—providing evidence coupled with clinical benefit to show clearing of amyloid from the brain. Selkoe added that the trials underway focusing on neutralizing or clearing amyloid are on the right track. This could potentially lead to clear-cut data that will be submitted to the FDA for approval of the first Alzheimer drug to slow the progress of disease.

In addition to the amyloid hypothesis, Selkoe mentions the interest surrounding the tau protein which is just as important as the Aβ problem and necessary to get clinical symptoms. If patients didn’t undergo tau alteration, Selkoe says, the Aβ problem wouldn’t produce memory failure.