Understanding the Complexity and Heterogenicity of Alzheimer Disease: Thomas Wisniewski, MD


The director of NYU Langone’s Alzheimer’s Disease Research Center and Center for Cognitive Neurology discussed current knowns and unknowns about the pathology of Alzheimer disease. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"It used to be that most of the preclinical and clinical trials were very much amyloid-centralized. Almost all targeted amyloid-ß on the plaque side of things, but in the last few years, that hasn’t been true. Diverse targets are being assessed.”

From 1995 to 2021, $42.5 billion in cumulative private expenditures funded clinical trials testing agents for Alzheimer disease (AD). At times, the field seemed to be on the brink of a breakthrough, with 57% of those costs coming from phase 3 trials.1 Nonetheless, aside from the 2021 approval of aducanumab (Adehelm; Biogen)­—which was met with controversy across neurology and medicine as a whole—there have only been 5 novel drugs, all for symptomatic treatment, to reach FDA approval in the past quarter century.

Over time, there have been hundreds of papers published seeking to further understand the root causes of the disease and thus produce more diversely targeted therapeutics. The complex nature of the disease, and the various pathogenic pathways it derives from, makes AD one of the most difficult diseases to crack, Thomas M. Wisniewski, MD, said. Wisniewski, director of NYU Langone’s Alzheimer’s Disease Research Center and Center for Cognitive Neurology, believes the community has gained an immense amount of knowledge regarding the disease’s pathology; however, finding effective therapies remains a challenge.

In an interview with NeurologyLive®, Wisniewski provided context on the advances in the understanding of AD, and the need to learn more about what drives the root its pathology. Additionally, he discussed the way drug development should be approached, the potential for combination approaches, and the difficulties finding drugs to treat the sporadic nature of the disease.

1. Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer disease: a retrospective exploration. Alzheimer Dement. Published online September 28, 2021. doi:10.1002/alz.12450
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