These familial forms are rare, but very aggressive and typically affect individuals before the age of 60. The findings jointly obtained by Dr. Safak Caglayan and Professor Thomas Willnow from the Max Delbrück Center (MDC) Berlin-Buch, Germany, and by Professor Junichi Takagi from the University of Osaka, Japan, have now been published in Science Translational Medicine, 10.1126/scitranslmed.3007747)*.
Currently, about 35 million people suffer from AD worldwide. Those afflicted are confronted with the loss of function and eventual death of their nerve cells, a process which leads to the progressive loss of memory and to dementia. Inheritable (familial) forms of AD are rare. “About 0.5 – 1 per cent,” Professor Willnow estimates. Still, familial forms of the disease are informative for science as they provide insight into the disease’s genetic causes, which probably also play a role in the sporadic form of AD. Sporadic AD is the common form of age-related dementia affecting the vast majority of patients, but its causes are still unclear.
The major culprit in the occurrence of AD is a short protein fragment called amyloid-beta peptide, or A-beta for short. A-beta is produced in the nerve cells from the amyloid precursor protein (APP), a larger protein that is cut into pieces by molecular scissors (secretases). The production of A-beta is a normal physiological process which occurs in the brain of every healthy human being. The reason for the production of A-beta is still a matter of debate, but recent findings suggest that this peptide reduces the activity of nerve cells in order to keep them from overreacting.
A-beta becomes a problem when too much is produced, as is the case in the brain of patients at risk of AD. Overproduction of this peptide impairs the communication between nerve cells, causing memory deficits and cognitive impairment. In addition, too much A-beta results in the deposit of plaques in the brain that damage nerve cells even further. “Since the amount of A-beta in the brain constantly rises with the age of the individual, the risk of developing AD increases dramatically in ageing societies,” Professor Willnow explains.Nerve cells produce protecting factor
“Genetic studies by many research groups around the world support this hypothesis,” says Professor Willnow. These studies show that specific gene variations of SORLA which cause reduced production of this protecting factor are more often seen in AD patients than in others. This observation suggests that the brain of some individuals produces too little SORLA. “Their risk of developing AD is higher,” Professor Willnow points out. He assumes that high levels of SORLA in the brain slow down the process of AD, whereas low levels of SORLA increase the risk of the disease.
*Lysosomal Sorting of Amyloid-b by the SORLA Receptor Is Impaired by a Familial Alzheimer’s Disease Mutation
Authors: Safak Caglayan1, Shizuka Takagi-Niidome2, Fan Liao3; Anne-Sophie Carlo1, Vanessa Schmidt1, Tilman Burgert1, Yu Kitago2, Ernst-Martin Füchtbauer4, Annette Füchtbauer4, David M. Holtzman3, Junichi Takagi2* and Thomas E. Willnow1*
Affiliations: 1Max Delbrück Center for Molecular Medicine, Berlin, Germany; 2Institute for Protein Research, Osaka University, Osaka, Japan; 3Department of Neurology, Washington University, and Department of Neurology, Hope Center for Neurological Disorders, St. Louis, US; and 4Department of Molecular Biology, Aarhus University, Aarhus, Denmark.Contact:
Barbara Bachtler | Max-Delbrück-Centrum
ARTORG and Inselspital develop artificial pancreas
26.11.2015 | Universitätsspital Bern
Laboratory study: Scientists from Cologne explore a new approach to prevent newborn epilepsies
24.11.2015 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
Before the fluid of the middle ear drains and sound waves penetrate for the first time, the inner ear cells of newborn rodents practice for their big debut. Researchers at Johns Hopkins report they have figured out the molecular chain of events that enables the cells to make “sounds” on their own, essentially “practicing” their ability to process sounds in the world around them.
The researchers, who describe their experiments in the Dec. 3 edition of the journal Cell, show how hair cells in the inner ear can be activated in the absence...
Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.
Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...
The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...
Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...
In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.
Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...
30.11.2015 | Event News
25.11.2015 | Event News
17.11.2015 | Event News
30.11.2015 | Earth Sciences
30.11.2015 | Life Sciences
30.11.2015 | Ecology, The Environment and Conservation