Brain study unlocks secrets of Alzheimer's
New ways of diagnosing and treating dozens of brain disorders could soon emerge from a pioneering study of the chemical and genetic makeup of the vital microscopic gaps between nerve cells that control all brain functions.
Scientists announced yesterday that they have identified more than a thousand proteins and their related genes which are involved in transmitting electrical messages from one nerve cell to another across the tiny gaps of the brain's many billions of synapses – switches that control brain activity.
The researchers said the feat could be compared to the deciphering of the human genome, because knowing the chemical and genetic makeup of the synapses will lead to important new insights into the nature of the many brain disorders that have so far defied adequate scientific explanation.
The study identified 1,461 proteins and their genes that make up the so-called "post-synaptic density" of chemicals that control the transmission of each electrical message from one nerve cell to another. The scientists also found that these proteins could be linked directly with 130 brain diseases, including Alzheimer's and Parkinson's.
The post-synaptic density is a complex collection of protein molecules that sticks out from the membrane of the second nerve cell of the synapse which receives the chemically transmitted message from the first nerve cell. Scientists believe that this assemblage of proteins is involved in many if not all major brain diseases.
Professor Seth Grant, of the Wellcome Trust Sanger Institute in Cambridge, said the discovery of the proteins would lead to new tests for diagnosing brain disorders at an earlier age than is currently possible, as well as opening the door to fundamentally different ways of developing drugs and therapies for effective treatments. "Our findings have shown that the human post-synaptic density is at centre stage of a large range of human diseases affecting many millions of people," Professor Grant said. "We found over 130 brain diseases involved the post-synaptic density – far more than expected.
"These diseases include common debilitating diseases such as Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders as well as epilepsies and childhood development diseases, including forms of autism and learning disability," he said.
The study, published in the journal Nature Neuroscience, involved analysing the many different proteins found in the synapses of tiny samples of brain tissue extracted from the outer brain cortex region of patients undergoing brain surgery at an Edinburgh hospital.
The scientists then compared the genetic sequences of the 1,461 proteins they found with the genetic sequences that have been linked with known brain disorders, leading them to directly associate the post-synaptic proteins with disorders of the brain or central nervous system. "We did not anticipate that so many diseases would involve the post-synaptic density. And it shows that many diseases that had previously had no obvious relationship with each other actually all act on the same set of proteins," he said.
"We know of no other molecular structure in the nervous system that has this many diseases or disease genes. Moreover, this number will increase as new DNA sequencing studies of disease proceed in coming years," he said.