Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Impaired clearance of amyloid-beta causes vascular damage in Alzheimer’s disease

21.07.2005


New research suggests that accumulation of amyloid-â peptides in cerebral blood vessels, as opposed to the brain itself, may be a more important pathological mediator of Alzheimer’s disease. Two independent yet related articles describe such findings in the August issue of The American Journal of Pathology. Both articles are highlighted on the Journal’s cover.



Alzheimer’s disease, the most common form of progressive dementia, affects an estimated 4.5 million Americans according to the Alzheimer’s Association. Amyloid-â (Aâ) deposition is a hallmark of Alzheimer’s disease and other cerebral amyloid angiopathies. However, exactly how Aâ accumulates and causes damage is not fully understood.

In the first article, "Cerebral microvascular Aâ deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant AâPP," Miao et al. describe early-onset Aâ deposition in Tg-SwDI mice. These mice express Aâ protein with mutations that are found in human early-onset cerebral amyloid angiopathy, causing specific accumulation of Aâ in cerebral blood vessels.


The Aâ peptides accumulated because they could not adequately cross the blood-brain barrier to be cleared from the brain. Over time, Aâ accumulation increased in the cerebral microvessels of the thalamus and subiculum of the brain. This resulted in degeneration of blood vessels as evidenced by reduced vessel density and increased apoptosis. Neuroinflammation also occurred as large numbers of microglia, along with inflammatory cytokines, were found at sites of Aâ accumulation.

The authors conclude that early-onset Aâ accumulation occurs predominantly in the cerebral microvasculature and appears largely responsible for the neuroinflammation in these mice. They also demonstrate the utility of Tg-SwDI mice in studying cerebral amyloid angiopathies, such as Alzheimer’s disease.

The second article, by Kumar-Singh et al., "Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer’s disease are centered on vessel walls," utilizes two different transgenic mice: Tg2576 and PSAPP. Both models produce dense-core plaques, highly concentrated deposits of Aâ, and were used to investigate the possible association of blood vessels with Aâ deposits.

In these mice, dense-core plaques associated with cerebral vessels with high specificity. There was also evidence of vessel damage and blood-brain barrier damage, resulting in release of Aâ through the vessel walls and accumulation of plaques next to the vessels. These data confirm previous observations in humans that senile plaques associate with blood vessels, especially in the vasculotropic Flemish type of Alzheimer’s disease.

The authors propose a model of dense-core plaque formation that is dependent on cerebral vessels. As Aâ is cleared from the brain, it exerts a cytotoxic effect on the endothelial cells of the vascular wall (a process that may be exacerbated if clearance is impaired). This leads to loss of vessel integrity and accumulation of Aâ in the area surrounding the compromised vessel wall. Eventually, the damage is so great that the blood vessel deteriorates beyond functional use and new vessels form to pick up the slack. The result is a multicentric dense-core plaque that associates with multiple vessels.

These studies describe several animal models for further examining the pathogenesis and treatment of Alzheimer’s disease and related cerebral amyloid angiopathies. And both studies confirm that Aâ generated by neurons accumulates in blood vessels following attempted clearance of excess Aâ peptides. Thus, study of novel therapies that reduce the blood vessel-associated deposition of Aâ may prove beneficial to patients with Alzheimer’s disease.

Audra Cox | EurekAlert!
Further information:
http://www.asip.org

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

Bodyguards in the gut have a chemical weapon

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>