Summary: Protein deposits from senile plaques affect the walls of blood vessels and alter their growth factor, causing dysfunction in the brain’s small blood vessels.
Source: University of Oslo
If the blood supply to your brain decreases, it can trigger Alzheimer’s disease. Scientists at UiO wanted to find out whether this leads to more or fewer blood vessels and what role one particular protein plays in such a process.
About 100,000 Norwegians suffer from dementia. Many of them have Alzheimer’s. The blood flow in the brain changes with Alzheimer’s disease.
“Nerve cells are destroyed and this must have something to do with the blood supply. Blood carries both oxygen and nutrients to the cells. The disease begins to develop long before patients get any symptoms—changes occur over 10 to 12 years before you notice that anything is wrong,” explains researcher and Associate Professor Reidun Torp at the Institute of Basic Medical Sciences.
She is interested in what is called “senile plaques” in the brain and how the brain rids itself of them. Plaque is a form of waste matter that comes from “incorrectly produced” proteins that build up as deposits in the brain.
“The essential key to discovering how to prevent Alzheimer’s disease is to find out how the brain handles this plaque before it is too late,” she says.
Destroys nerve tissue in the brain
Torp and other researchers at the Department of Molecular Medicine have tried for many years to solve the puzzle of the various changes that occur in the brain. Their research represents stepping-stones on the way towards treating Alzheimer’s or preventing the disease.
One of the things Torp has studied is how particular proteinaceous fibers twist around each other in tangles and destroy brain cells.
“With Alzheimer’s, there is a connection between these two processes: the fibers that twist around each other and the senile plaque, which together result in the destruction of nerve tissue in the brain. They block the communication between nerve cells and disrupt the processes that nerve cells need to survive. We know a good deal about these two processes but this isn’t much help if we can’t stop it happening in the brain,” she says.
Unchanged density of blood vessels
Earlier research has shown that several of the same risk factors behind the development of cardiovascular disease also can lead to Alzheimer’s. In order to see the connection between the disease and the blood supply to the brain, the researchers wanted to find out whether the density of small blood vessels in the brain decreases, increases or remains unchanged in a patient with Alzheimer’s.
Her research team recently published an article in the Journal of Alzheimer’s Disease.
Two of the methods used by the researchers were various microscopy techniques and biochemical analyses. Research fellow Gry Syverstad Skaaraas is the lead author of the study.
“We found that the density of blood vessels was unchanged in mice that had a lot of senile plaque, compared to mice without plaque,” she says. “What we found instead was that the protein deposits from the plaque affected the walls of the blood vessels and changed their growth factors, which would indicate that the vessels no longer function as they should.”
Growth factors are proteins that break down and form new blood vessels in the brain. We believe that it is this process that is disrupted in Alzheimer’s disease, says Torp.
Probably at a turning point towards finding a better treatment
According to the researchers, the study led to several new discoveries. One was that a type of cells called pericytes are destroyed by senile plaques in the blood vessels. Pericytes lie partly round the smallest blood vessels, allowing these to contract and regulate the blood stream in the brain.
Torp points out that a great deal of research is being carried out into Alzheimer’s and she can see a lot of positive signs.
“I think we are at a turning point towards finding a better treatment,” she says.
About this Alzheimer’s disease research news
Author: Press Office
Source: University of Oslo
Contact: Press Office – University of Oslo
Image: The image is in the public domain
Original Research: Open access.
“Cerebral Amyloid Angiopathy in a Mouse Model of Alzheimer’s Disease Associates with Upregulated Angiopoietin and Downregulated Hypoxia-Inducible Factor” by Gry H.E. Syverstad Skaaraas et al. Journal of Alzheimer’s Disease
Cerebral Amyloid Angiopathy in a Mouse Model of Alzheimer’s Disease Associates with Upregulated Angiopoietin and Downregulated Hypoxia-Inducible Factor
Vascular pathology is a common feature in patients with advanced Alzheimer’s disease, with cerebral amyloid angiopathy (CAA) and microvascular changes commonly observed at autopsies and in genetic mouse models. However, despite a plethora of studies addressing the possible impact of CAA on brain vasculature, results have remained contradictory, showing reduced, unchanged, or even increased capillary densities in human and rodent brains overexpressing amyloid-β in Alzheimer’s disease and Down’s syndrome.
We asked if CAA is associated with changes in angiogenetic factors or receptors and if so, whether this would translate into morphological alterations in pericyte coverage and vessel density.
We utilized the transgenic mice carrying the Arctic (E693G) and Swedish (KM670/6701NL) amyloid precursor protein which develop severe CAA in addition to parenchymal plaques.
The main finding of the present study was that CAA in Tg-ArcSwe mice is associated with upregulated angiopoietin and downregulated hypoxia-inducible factor. In the same mice, we combined immunohistochemistry and electron microscopy to quantify the extent of CAA and investigate to which degree vessels associated with amyloid plaques were pathologically affected. We found that despite a severe amount of CAA and alterations in several angiogenetic factors in Tg-ArcSwe mice, this was not translated into significant morphological alterations like changes in pericyte coverage or vessel density.
Our data suggest that CAA does not impact vascular density but might affect capillary turnover by causing changes in the expression levels of angiogenetic factors.