Redefining the Understanding of Alzheimer Disease and Its Pathology: Ralph Nixon, MD, PhD


The professor of psychiatry and cell biology at NYU Langone provided commentary on new findings which challenge traditional theories on the root of Alzheimer disease and how it is targeted. [WATCH TIME: 17 minutes]

WATCH TIME: 17 minutes

"In the case [that] we’re correct—I think the pathology speaks for itself—there’s little logic in removing the amyloid on the outside because the cell has been so compromised and it’s going to die. There’s no reason to remove the amyloid on the outside because it originated from, basically, a dying cell."

In early June 2022, a group of investigators published a study of Alzheimer disease (AD) mouse modelsthat identified neuronal damage taking place inside cells well before thread-like amyloid plaques form and clump together. Led by Ralph Nixon, MD, PhD, the study traced the root dysfunction to the brain cells’ lysosomes, which are filled with acidic enzymes involved in the routine breakdown, removal, and recycling of metabolic waste from everyday cell reactions, as well as from the disease.

The findings also showed heavily damaged and destined for death neurons pooled together in “flower-like” patterns, bulging out from the cells’ outer membranes and massing around each cell’s center, or nucleus. Above all, the new research challenged traditional drug development approaches taken by industry leaders, who, in recent years, have developed agents that specifically target amyloid plaques. Nixon, a professor of psychiatry and cell biology at NYU Langone, believes this research answers for why these agents have failed.

In an interview with NeurologyLive®, Nixon provided in-depth detail on the results of the study, including the specific immunologic and pathologic changes seen in these mouse models. He discussed how the community has previously perceived the disease and why these findings may change how drug development is approached.

1. Lee J, Yang D. Goulbourne CN, et al. Fault autolysosome acidification in Alzheimer’s disease mouse models incudes autophagic build-up of AB in neurons, yielding senile plaques. Nature. 2022;25:688-701. doi:10.1038/s41593-022-01084-8
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