Diving deep into Alzheimer’s data sets, a recent Emory Brain Health Center paper in Nature Genetics spots several new potential therapeutic targets, only one of which had been previous linked to Alzheimer’s. The Emory analysis was highlighted by the Alzheimer’s site Alzforum, gathering several positive comments from other researchers.

Lead author Thomas Wingo and his team — wife Aliza Wingo is first author – identified the targets by taking a new approach: tracing connections between proteins that are altered in abundance in patients’ brains and risk genes identified through genome-wide association studies.

The list of 11 genes/proteins named as “consistent with being causal” may be contributing to AD pathogenesis through various mechanisms: vesicular trafficking, inflammation, lipid metabolism and hypertension. We asked Wingo which ones he wanted to highlight, and he provided this comment:

“The most interesting genes, to me, are the ones involved in the SNARE complex (in the paper, STX4 and STX6) and the others involved in vesicular trafficking. There is already a deep body of literature that describe a role for some of these components in AD, and I’m hopeful providing specific targets might be useful to those studies.”

A simplistic way to look at the mechanism of Alzheimer’s disease is: proteins build up in the brain, in the form of amyloid plaques and neurofibrillary tangles. The functions of neurons and other brain cells are thought to be impaired by bits of beta-amyloid floating around.

Inside neurons, the SNARE complex is the core of the machinery that pushes vesicles to fuse with the cell membrane. Neurons communicate with each other by having vesicles inside the cell – bags full of neurotransmitters – release their contents. They’re like tiny packets of pepper or other spices that make the neuron next door sneeze. In Alzheimer’s, amyloid oligomers have been reported to block SNARE complex assembly, which may explain aspects of impaired cognition.