By: Judy Zhao, Class of 2029
Figure 1. Image of a white rat, often used as a model organism in basic scientific experiments
One of the most significant pathological hallmarks of Alzheimer’s disease (AD) is the buildup of amyloid-beta (Aβ) plaque in the brain. A study conducted by Dr. Kim and colleagues at Stony Brook University investigated the association between brain blood flow and the earliest stages of AD, before high levels of Aβ plaque form. Their aim was to determine whether disruptions in brain blood flow could occur before any Aβ accumulates and identify whether these signs could be used to catch early signs of AD.
The brain’s ability to increase blood flow, known as functional hyperemia, supplies it with oxygen and nutrients while clearing metabolic waste. Mice, which share a large fraction of their genes with humans, exhibited abnormally prolonged increases in blood flow when modeling AD, even before Aβ levels were detectable. The control group of healthy mice showed only temporary increases in blood flow, which eventually returned to baseline levels.
Prolonged levels of hyperemia were most likely due to increased activity in inhibitory neurons from the hippocampus, a brain region responsible for forming new memories and supporting learning. If the neurons remained active for too long, it would drive continuous blood flow through nitric oxide (NO) signaling pathways. This prolonged activity would disrupt both brain homeostasis and normal neural signaling, and could eventually increase Aβ buildup.
After investigating the progression of AD and observing Aβ accumulation, the pattern of brain blood flow was reversed, demonstrating a rapid decline in functional hyperemia. Mirroring the development in humans diagnosed with AD, this change suggests that the neurovascular system undergoes exhaustion. Constant overactivity could damage and desensitize mechanisms that would usually regulate blood vessel dilation. This results in the brain losing its ability to properly match blood flow to neural activity, also known as neurovascular coupling. In the hippocampus, without sufficient blood flow, neurons become energetically depleted, which accelerates the neurodegeneration commonly seen in AD.
In this study, Dr. Kim and colleagues reveal that the disruptions in brain blood flow are not just a result of AD, but could be early indicators of AD onset. This highlights how early vascular dysfunction influences protein buildup and declines in neural activity, and researchers can consider new approaches to intervention. By targeting abnormal blood flow before irreversible damage occurs, there is potential to either delay or prevent further development of AD.
Work’s Cited:
[1] Kim, T. A., Cruz, G., Syty, M. D., Wang, F., Wang, X., Duan, A., Halterman, M., Xiong, Q., Palop, J. J., & Ge, S. (2025). Neural circuit mechanisms underlying aberrantly prolonged functional hyperemia in young Alzheimer’s disease mice. Molecular psychiatry, 30(2), 367–378. https://doi.org/10.1038/s41380-024-02680-9
[2] Image retrieved from: https://unsplash.com/photos/a-white-rat-sitting-on-top-of-a-wooden-table-6N8apSPm6Ak
