Some Brain 'Pathways' Possibly Tied to Alzheimer's
Findings could point to new drug targets for dementia, although any treatment is still far away
"APOE4 changes the behavior of [the genes] SV2A and RFN219," said Abeliovich. "They go from good cops to bad cops, and amyloid precursor protein and other proteins end up in unfortunate parts of the cell, where they are processed into amyloid beta," he said.
A build-up of amyloid beta protein in the brain is a well-known hallmark of Alzheimer's disease.
One expert not involved in the research said the findings give scientists an important new clue to the Alzheimer's puzzle.
"The role of APOE4 in enhancing Alzheimer's risk has been a vexing problem for 20 years. The gene robustly increases amyloid buildup in mouse models but no consistent molecular or cellular explanation has emerged," explained Dr. Sam Gandy, director of the Mount Sinai Center for Cognitive Health in New York City.
Gandy said the new study now shows that APOE4 causes perturbations in the processing of amyloid precursor proteins inside cells and these perturbations "apparently cause nerve cells to make too much amyloid."
In an extra step, researchers tried blocking the action of SV2A with a drug called levetiracetam, which is used to treat seizures. In that experiment, cells in a petri dish processed the amyloid precursor protein more normally -- even in the presence of APOE4.
The finding suggests the medication could play a role in the prevention of the disease, though researchers say much more research is needed to confirm their results.