Memory loss and cognitive dysfunction, two hallmarks of Alzheimer’s disease, have now been linked to low levels of one particular protein, called NPTX2. The discovery represents a stepping-stone in the mechanisms underlying this disease, which may help in the development of new therapies. The study, “NPTX2 and cognitive dysfunction in Alzheimer’s Disease,” was published in the journal eLife. Amyloid is a protein known to accumulate in the brain of Alzheimer's patients, forming amyloid plaques. These protein clumps are thought to underlie the mental decline associated with the disease. However, studies imaging the brain and post-mortem analyses of brain tissue show that high levels of amyloid can occur without Alzheimer's symptoms. These results challenge the proposed direct link between amyloid deposits in the brain and dementia. Now, Johns Hopkins Medicine researchers and colleagues have shown that when low levels of the protein NPTX2 occur in the brain at the same time as amyloid is accumulating, it causes a disruption in the connection of neurons, leading to a failure of memory. "These findings represent something extraordinarily interesting about how cognition fails in human Alzheimer's disease," Paul Worley, MD, a neuroscientist at Johns Hopkins University School of Medicine and the study's lead author, said in a press release. "The key point here is that it's the combination of amyloid and low NPTX2 that leads to cognitive failure."