The brains of individuals with Alzheimer's disease contain protein aggregates called plaques and tangles, which interfere with normal communication between nerve cells and cause progressive learning and memory deficits. Now, a research team led by Takaomi Saido from the RIKEN Brain Science Institute in Wako has identified a particular fragment of the amyloid precursor protein (APP) that contributes to the formation of plaques in the brain1.
Enzymes cut APP to form shorter protein fragments and, in Alzheimer's patients, these sticky fragments clump together to form amyloid plaques. Most current research on this disease focuses on a 42 amino acid-long fragment called Aâ42, in part because other researchers had shown that APP mutations that increase Aâ42 cause Alzheimer's disease in some families. Other APP fragments are also found in the brain of individuals with Alzheimer's disease, but their role in disease was unclear.
Saido and colleagues studied a 43 amino acid-long fragment called Aâ43 because other groups have shown that it can form aggregates as readily as Aâ42 (Fig. 1). The researchers generated mice that have a mutation in the presenilin-1 gene that contributes to the cleavage of APP, and showed that it led to increased formation of Aâ43 in cell culture experiments.
The research team then mated these presenilin-1 mutant mice to APP mutant mice, which display many symptoms of Alzheimer's disease, such as deposition of plaques in the brain and a gradual loss of memory. APP mutant mice generally exhibit plaque formation at one year of age. However, with the increase in Aâ43 caused by the presence of the presenilin-1 mutation, these so-called 'double-mutant mice' had plaques in their brain six months earlier than usual. The double-mutant mice also seemed to show memory deficits at an even earlier age than APP mutant mice. Furthermore, the research team showed that Aâ43 is even more prone to aggregate and to cause neuronal damage than is Aâ42.
The findings therefore suggest that Aâ43 plays a role in accelerating Alzheimer's disease. Saido and colleagues argue that therapies that specifically prevent Aâ43 accumulation, such as by enhancing the cleavage of Aâ43 into shorter Aâ fragments, or by stimulating the immune system to clear Aâ43, could therefore be beneficial in slowing the progression of Alzheimer's disease.
“Aâ43 could also be a diagnostic marker for Alzheimer's disease,” explains Takashi Saito, the first author of the study. “We would now like to develop it along these lines.”
The corresponding author for this highlight is based at the Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute
First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife
Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
25.10.2016 | Earth Sciences
25.10.2016 | Power and Electrical Engineering
25.10.2016 | Process Engineering