Luke Putelo ’25, Neuroscience, 22X

Figure: Histopathologic picturing of senile plaques seen in the cerebral cortex in a patient with presenile onset of Alzheimer disease

Image Source: Wikimedia Commons

For years, Alzheimer’s Disease (AD) has stumped researchers; while techniques and procedures have been developed to mitigate the disease, a cure long seemed unattainable. Instead, many would refer to the condition as an unavoidable part of aging and may only be delayed or dampened.

However, a recent study at the University of Kansas has shown preliminary results that display reduced AD phenotype expression within mice (Smith et al., 2022). The same team had done similar studies a few years prior but re-upped with a new approach. They began by introducing a methionine sulfoxide-rich protein to four-month-old mice that had been genetically modified to possess a genotype in the same family structure as that of AD. The researchers then observed their immune reactions and their memory systems over the course of multiple memory tests. After a six-month period, it was found that the AD mice who had been injected with methionine sulfoxide protein had immune system responses that produced antibodies capable of reducing the likelihood of AD phenotype expression (Smith et al., 2022).

The study found the modified mice to have greater short-term memory capacity and recollection abilities when compared to the control subjects. The researchers’ expectations relied on the condition that mice would spend more time experiencing a new environment than they had already experienced. The modified mice spent much more time in these new environments when compared to the non-modified mice. Because one of the major brain functions diminished by the presence of Alzheimer’s disease is short-term memory, mice expressing greater short-term memory is a promising result that the protein may decrease AD expression (Smith et al., 2022).

A subsequent test examined long-term memory retention and memory retrieval over a six-day period. The mice were exposed to a Morris water maze, a water bath with a uniform platform that sits just below the water level to reduce the likelihood of sight playing a major role. The maze is intended to test the mice’s ability to recognize what region of the water bath holds the platform; eventually, all mice find the platform location. However, the protein-immunized mice found the platform at a much faster rate. In subsequent days, this result continued; the injected mice were more capable of finding the platform than the control mice. To confirm the influence of memory in this experiment and reduce the likelihood of vision playing a role in the rate at which the platform was found, the researchers removed the platform from the maze. The injected mice spent more time in the vicinity of the formerly present platform when compared to the control mice (Smith et al., 2022).

These experiments offer promising results that a similar protein structure could be administered via vaccine to delay the onset of and/or immunize against Alzheimer’s disease.  The protein would be injected as it was with the mice and shares a similar scientific basis with the Covid-19 vaccine; an AD vaccine could be given and followed by booster shots. The vaccine would allow the body to form its own antibodies against AD rather than introducing antibodies into the body, which could have severe side effects. The researchers see their next step as being pre-clinical and clinical trials in humans (Smith et al., 2022).

References

Adam S. Smith[AG10] , Kyle R. Gossman, Benjamin Dykstra, Fei Philip Gao, Jackob Moskovitz. Protective Effects against the Development of Alzheimer’s Disease in an Animal Model through Active Immunization with Methionine-Sulfoxide Rich Protein Antigen. Antioxidants, 2022; 11 (4): 775 DOI: 10.3390/antiox11040775

University of Kansas. (2022, May 3). Study preserves memory in mice, offering promising new basis for active immunization against Alzheimer’s disease. ScienceDaily. Retrieved May 22, 2022 from www.sciencedaily.com/releases/2022/05/220503141332.htm