Cleveland Clinic researchers have identified a brain protein that may play a key role in the memory loss associated with Alzheimer’s disease


Cleveland Clinic researchers have identified a brain protein that may play a key role in the memory loss associated with Alzheimer’s disease, according to a study published online Sunday in the journal Nature Neuroscience. The discovery, part of a wider body of work in an area of brain research called microglia inflammation, has pointed to connections between diseases such as Alzheimer’s, multiple sclerosis, neuropathic pain and Parkinson’s disease. The brain protein, called Neuroligin-1 (NLGN1), has previously been associated with long-term memory formation, and when damaged is linked to cognitive diseases such as autism. In current models of Alzheimer’s disease, researchers believe that sticky protein plaques, called amyloid beta, accumulate in the brain, overwhelming the brain’s natural defense and immune system—the microglia. When the microglia can’t clear out the protein plaques fast enough, they become inflamed. When that happens, “it’s responsible for many disease processes like Alzheimer’s or other neuro-inflammatory conditions like neuropathic pain, multiple sclerosis, you name it,” said Dr. Mohamed Naguib, an anesthesiologist at the Clinic and senior author of the study. The inflammation leads to gene modifications in the brain, and one of the affected proteins is NLGN1. Tampering with NLGN1 leads to problems with the synapses, the spaces between brain cells that allow neurons to pass messages along. Malfunctioning synapses mean missed messages, and memory problems. “If we prevent microglia inflammation, we can preserve the synaptic function and preserve the memory,” said Naguib, whose research group has been working on studies of a drug, called MDA7, which may be able to accomplish just this. Naguib's group did not use MDA7 in the current study, which involved mice and rats, but they have used it to prevent neuropathic pain during chemotherapy treatment in animals, which Naguib said triggers the same inflammatory process. It was neuropathic pain, a chronic pain that involves nerve injury, which first brought the group of anesthesiologists to study microglia inflammation. “It became apparent as our research went on how important that inflammation was to a wide variety of disease processes, which then led to following the Alzheimer’s path,” said Dr. Joseph Foss, Director, Clinical Research for General Anesthesiology at the Clinic and a member of the research team working to move MDA7 forward. “Our next step really is to try to raise enough funding to get [MDA7] into humans,” said Dr. David Brown, chairman of the Clinic’s anesthesiology institute and another author of the study. “To date Alzheimer’s has been a very difficult disease to treat, and it touches just about every family in the country in one way or another.” Brown believes that targeting microglia inflammation may have even more disease applications than they currently know.