The research team investigated a protein in the brain called neural cell adhesion molecule 2, or NCAMP2, a family of molecules that connect the membranes of synapses and helps to stabilize the long lasting synaptic contacts between neurons.
“One of the first signs of Alzheimer’s disease is the loss of synapses – the structures that connect neurons in the brain,” said study leader, Dr Vladimir Sytnyk, of the UNSW School of Biotechnology and Biomolecular Sciences.
“Synapses are required for all brain functions, and particularly for learning and forming memories. In Alzheimer’s disease, this loss of synapses occurs very early on, when people still only have mild cognitive impairment, and long before the nerve cells themselves die.
“We have identified a new molecular mechanism which directly contributes to this synapse loss – a discovery we hope could eventually lead to earlier diagnosis of the disease and new treatments.”
The researchers analyzed post-mortem brain tissue from people with and without the condition, and they discovered that synaptic NCAM2 levels in the part of the brain known as the hippocampus were low in those with Alzheimer’s disease. NCAM2 was broken down by another protein called beta-amyloid; the main component of the plaques that build up in the brains of people with the disease.
“Our research shows the loss of synapses is linked to the loss of NCAM2 as a result of the toxic effects of beta-amyloid,” said Dr Sytnyk.
Aβ-dependent reduction of NCAM2-mediated synaptic adhesion contributes to synapse loss in Alzheimer’s disease, Vladimir Sytnyk et al., Nature Communications, doi:10.1038/ncomms9836, published online 27 November 2015.