Summary: New research shows that a shorter form of the amyloid‑beta protein, Aβ1‑40, accumulates in the walls of small brain arteries, reducing blood flow and potentially contributing to memory loss in Alzheimer’s disease.
Source: University of Manchester
A team at the University of Manchester reports a significant advance in understanding how Alzheimer’s disease affects the brain’s blood vessels. Their study, published in Proceedings of the National Academy of Sciences (PNAS), identifies a mechanism by which the amyloid‑beta fragment Aβ1‑40 narrows small surface arteries of the brain, reducing blood flow and potentially worsening cognitive decline.
Alzheimer’s disease is commonly associated with the build‑up of amyloid‑beta protein in the brain, where it forms plaques that damage neurons. Increasingly, research points to vascular changes as another important contributor to the disease. However, the precise way in which amyloid proteins affect blood vessels has been unclear.
The Manchester researchers focused on pial arteries, the small arteries that run across the surface of the brain and play a key role in regulating cerebral blood flow and oxygen delivery. Proper function of these arteries is essential for supplying nutrients to brain tissue; sustained narrowing can deprive regions of the brain of oxygen and glucose, impairing cognitive function and contributing to the memory loss often seen in Alzheimer’s patients.
In experiments with aged mice engineered to produce excess Aβ1‑40, the investigators observed that pial arteries were significantly narrower than those in healthy control animals. Further experiments showed that this narrowing results from Aβ1‑40 interfering with a vascular protein, the large conductance calcium‑activated potassium channel known as BK. Under normal conditions, BK channels help blood vessels relax and widen; when BK signaling is blunted, vessels constrict and blood flow falls.
To test direct effects of the peptide, the team exposed healthy pial arteries to Aβ1‑40 and measured BK channel activity after one hour. The peptide weakened BK‑mediated signals, producing vasoconstriction in otherwise healthy arteries. These findings support a model in which accumulation of Aβ1‑40 in arterial walls disrupts BK channel function and reduces cerebral blood flow.
The researchers plan to pinpoint which segment or structural feature of Aβ1‑40 is responsible for blocking BK channels. Identifying that interaction site could enable development of drugs that prevent Aβ1‑40 from disabling BK signaling, preserving arterial dilation and maintaining blood flow to vulnerable brain regions. Such treatments would represent a vascular‑targeted approach to slowing or preventing progression of Alzheimer’s disease.
Dr. Adam Greenstein, lead researcher and Clinical Senior Lecturer in Cardiovascular Sciences at the University of Manchester, noted that past therapeutic efforts have largely targeted neurons and over 500 candidate drugs have been trialed without delivering an effective cure. By revealing a concrete mechanism by which Alzheimer’s affects small blood vessels, this work opens new avenues for therapy focused on preserving vascular health in the brain.
Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, commented on the broader importance of the findings, highlighting the urgent need for new strategies as the number of people living with dementia rises with an aging population. Vascular‑focused interventions—if translated into safe and effective drugs—could provide a desperately needed addition to the therapeutic options for this devastating condition.
About this Alzheimer’s disease research news
Author: Press Office
Source: University of Manchester
Contact: Press Office – University of Manchester
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Original Research: The findings are reported in Proceedings of the National Academy of Sciences (PNAS)