Alzheimer’s disease researchers have been working for a while with a small, sticky protein fragment, beta amyloid, that clumps into balls in the brains of patients with this degenerative neurological disease. It is a normal protein that is present in every normal brain but in Alzheimer’s it starts to accumulate into these balls or plaques. On build-up of amyloid symptoms of the disease appear.
In a new study this ‘over-production leading to plaque theory’ was negated. A person with Alzheimer’s seems to produce normal amounts of amyloid but cannot ‘drain’ them causing accumulation. Now if scientists can improve drainage of these protein they may be able to help patients. In normal amounts amyloid acts as a circuit breaker to prevent nerve firing from getting out of control. But too much amyloid can shut down nerves, eventually leading to cell death. That means that if amyloid levels were reduced early in the disease the damage might be reversed.
Richard Mohs, Alzheimer’s group team leader at Eli Lilly hopes for new therapeutic avenues from this study. He said, “We are much closer and quite optimistic that we will be able to do it.” Dr. Randall Bateman and Dr. David M. Holtzman, a neurology professor together explored the question to find these results that were published online Thursday by Science.
Dr. Bateman examined volunteers in their thirties and forties and checked on the level of amyloid in their cerebrospinal fluids. He noted that in Alzheimer’s patients beta amyloid was draining at a rate that is 30 percent slower than in healthy people the same age. Dr. Bateman said, “What we think may be happening is that a clearance mechanism is broken first.”
Dr. Roberto Malinow of the University of California, San Diego earlier looked at how beta amyloid affects synapses, the functional connections between nerve cells. He found that with over production of the protein signals were muffled. Another protein tau is an integral part of normal cells. It becomes tangled and twisted in Alzheimer’s, after cells are already dying. Tau facilitates beta amyloid’s lethal effects say researchers led by Dr. Lennart Mucke, a neurology professor at the University of California, San Francisco, and director of the Gladstone Institute of Neurological Disease.
In another study researchers found that boosting levels of CREB-binding protein (CBP), a protein needed to create long-term memories can reverse memory loss in mice with Alzheimer's disease. Salvatore Oddo of the University of Texas Health Science Center in San Antonio who led the study that appears in the in Proceedings of the National Academy of Sciences said, “We can reverse the learning and memory deficits by increasing the level of this protein called CBP.” He boosted CBP in mice that increased levels of yet another protein called brain-derived neurotrophic factor or BDNF, proteins needed to develop long-term memory. Oddo said, “In a mouse that develops symptoms like Alzheimer’s disease, these proteins are not activated… They may account for the memory impairment in these mice.” Thy used a harmless virus to deliver the protein. Alzheimer's mice that had been given the protein performed as well as healthy mice. Oddo said, “They showed no memory problems whatsoever. They learned the task they were supposed to learn, and when we probed for memory, they remembered what they learned the day before.” “Pharmaceutical companies could theoretically work toward finding a new drug that may facilitate the expression of this CBP protein,” he added.
In yet another study researchers noted that problems with blood flow in Alzheimer’s patients could lead to better treatment of the disease. Scientists from the University of Bristol, supported by the Alzheimer’s Research Trust, found marked abnormalities in blood flow regulation in Alzheimer’s patients. They noted that an enzyme that helps to control blood flow and the leakiness of blood vessel walls had increased activity in those with Alzheimer’s. Professor Seth Love, one of the researchers said that this angle had not been studied before. He added, “These findings give us hope for future research – there are already drugs available that might prove beneficial, and we should look to trial them.”