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
UNC Team uses cellular bubbles to deliver Parkinson's meds directly to brain
05.05.2015 | University of North Carolina at Chapel Hill
Receptor provides a surprise
04.05.2015 | Julius-Maximilians-Universität Würzburg
Texas A&M University researchers demonstrate how a narrow-band strobe light source for speckle-free imaging has the potential to reveal microscopic forms of life
In modern microscope imaging techniques, lasers are used as light sources because they can deliver fast pulsed and extremely high-intensity radiation to a...
A team of highly determined high school students discovered a never-before-seen pulsar by painstakingly analyzing data from the National Science Foundation's...
Scientists from Nepal, Switzerland and Germany was now able to show how erosion processes caused by the monsoon are mirrored in the sediment load of a river crossing the Himalaya.
In these days, it was again tragically demonstrated that the Himalayas are one of the most active geodynamic regions of the world. Landslides belong to the...
A world-class prime systems integrator and electronic systems provider known for its rapid, innovative, and agile technology solutions, Sierra Nevada Corporation (SNC) is currently developing a new space transportation system called the Dream Chaser.
The ultimate aim is to construct a multi-mission-capable space utility vehicle, while accelerating the overall development process for this critical capability...
Today, textiles are used for more than just clothes or bags – they are high tech materials for high-tech applications. High-tech textiles must fulfill a number of functions and meet many requirements. That is why the Fraunhofer Institute for Silicate Research ISC dedicated some major developing work to this most intriguing research area. The result can now be seen at Techtextil trade show in Frankfurt from 4 to 7 May. On display will be novel textile-integrated sensors, a unique multifunctional coating system for textiles and fibers, and textile processing of glass, carbon, and ceramics fibers to fiber preforms.
Thin materials and new kinds of sensors now make it possible to integrate silicone elastomer sensors in textiles. They are suitable for applications in medical...
05.05.2015 | Event News
23.04.2015 | Event News
23.04.2015 | Event News
05.05.2015 | Materials Sciences
05.05.2015 | Earth Sciences
05.05.2015 | Earth Sciences