New York:An experiment with genetically engineered mice has revealed how Alzheimer's can cause dementia in humans, say promising research. Using a genetically engineered mouse model mimicking the development of Alzheimer's disease in humans, researchers from Johns Hopkins University determined that a one-two punch of major biological "insults" must occur in the brain to cause dementia that is a hallmark of the disease. For decades, Alzheimer's disease, the most common cause of dementia, has been known to be associated with the accumulation of neuro-fibrillary tangles -- consisting of abnormal clumps of a protein called tau inside brain nerve cells. “In Alzheimer's disease, tau bunches up inside the nerve cells and beta-amyloid clumps up outside these cells, mucking up the nerve cells controlling memory,” said Philip C Wong, Professor of Pathology at Johns Hopkins. “What hasn't been clear is the relationship and timing between those two clumping processes, since one is inside cells and one is outside cells,” added lead author Tong Li, assistant professor of pathology at Johns Hopkins. New research suggests that the accumulation of beta-amyloid in and of itself is insufficient to trigger the conversion of tau from a normal to abnormal state. “For the first time, we think we understand that the accumulation of amyloid plaque alone can damage the brain but that's actually not sufficient to drive the loss of nerve cells or behavioural and cognitive changes," Wong explained. "What appears to be needed is a second insult -- the conversion of tau -- as well,” he added in a paper published in the journal Nature Communications. In humans, the lag between development of the beta-amyloid plaques and the tau tangles inside brain nerve cells can be 10 to 15 years or more. The work suggests that combination therapy designed to prevent both the beta-amyloid plaque formation as well as pathological conversion of tau may provide optimal benefit for Alzheimer's disease. “Our mouse model could be used to test new therapies,” the authors noted.