Trafficking Protein Helps Clear Amyloid-β From Brain

A protein in brain blood vessels called PICALM may help flush out amyloid-β—the peptide associated with Alzheimer’s disease—into the bloodstream, suggesting a possible new therapeutic target for the disease. Berislav V. Zlokovic of the University of Southern California and colleagues studied PICALM, in part, because single-nucleotide variations in the gene that encodes PICALM have been linked to an increased risk of developing Alzheimer’s. Zlokovic’s team found that the brains of patients with advanced Alzheimer’s had significantly lower levels of PICALM compared with those of healthy people (Nat. Neurosci. 2015, DOI: 10.1038/nn.4025). And PICALM levels in Alzheimer’s-affected brains correlated inversely with the amount of amyloid-β and extent of disease progression. To study the protein’s role further, the researchers genetically engineered mice so they had only one copy of the PICALM gene. Compared with normal mice, these animals accumulated more amyloid-β in their brains. On the basis of data from a series of cell microscopy experiments, the scientists think that, in cells lining brain blood vessels, PICALM helps pull in amyloid-β from the brain and then passes the peptide off to cellular machinery that spits it out into the bloodstream.