Dennis Selkoe, MD

“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 

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.

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Selkoe spoke to a number of topics in the Alzheimer space, including the challenges in the field and his excitement for the future.

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

“We think those oligomers are the principal toxic form of AB in Alzheimer disease, they’re neurotoxic.”

At the 2018 Alzheimer’s Association International Conference held in Chicago, Illinois, Dennis Selkoe, MD, presented the results from an exploratory analysis on crenezumab from the completed phase II BLAZE and ABBY clinical trials that showed the impact of crenezumab treatment throughout the duration on beta amyloid oligomer levels in cerebrospinal fluid (CSF) in subjects with mild to moderate Alzheimer disease.

The 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 with 

to discuss the results in further detail.

Researchers used an ultrasensitive in-house immunoassay to measure Aβ oligomer levels in CSF from 104 subjects from the ABBY and BLAZE trials before and after treatment with crenezumab versus placebo. Subjects received subcutaneous 300 mg crenezumab or placebo every 2 weeks or intravenous crenezumab (15 mg/kg) or placebo every 4 weeks for 68 weeks.

The results showed that treatment with crenezumab was associated with a consistent decrease in Aβ oligomer levels in the CSF; specifically, 86% of subjects receiving treatment intravenously and 89% receiving subcutaneous treatment had lower levels of Aβ oligomeric levels at week 69 than baseline. The difference in proportions of subjects with decreasing levels was significant for both treatment arms— 

= .01 for intravenous crenezumab versus placebo.

This is the first time anyone has shown direct evidence of target engagement of toxic forms of amyloid in humans, Selkoe noted, and these results strongly suggest target engagement, recommending assaying CSF Aβ oligomers in future trials.

The safety and efficacy of crenezumab is currently being evaluated in 2 phase III clinical trials, CREAD 1 and CREAD 2, studying 750 subjects in each trial with prodromal or mild Alzheimer disease.

The results conclude that treatment with crenezumab was associated with a consistent decrease in Aβ oligomer levels in the CSF.

Dennis Selkoe, MD

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

Dennis Selkoe, MD: Crenezumab Significantly Reduces Aβ Oligomers in CSF

Dennis Selkoe, MD

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

Dennis Selkoe, MD: Crenezumab Significantly Reduces A&#946; Oligomers in CSF

Dennis Selkoe, MD: Crenezumab Significantly Reduces Aβ Oligomers in CSF