Deposits of Protein Linked to Alzheimer’s

Two studies add to evidence that deposits of toxic protein in the brain produce symptoms of Alzheimer’s disease, an idea with implications for new treatments.

Deposits containing a protein called beta amyloid are hallmarks of the disease. But scientists disagree whether they cause symptoms of Alzheimer’s or are merely results of the disease process.

The question is important because if the deposits cause the mental decline of Alzheimer’s, then medicines aimed at preventing their formation or blocking their effect on brain cells would be helpful.

In the new work, scientists studied the effect of mutations in a gene called presenilin 1. In people, mutations of this gene cause a rare form of Alzheimer’s that is inherited. Most Alzheimer’s is not inherited, and the cause of non-inherited Alzheimer’s is a mystery.

In the Oct. 24 issue of the journal Nature, researchers report that mice given a mutated version of presenilin 1 produce double the usual amount of a particular version of beta amyloid in their brains, a version that is especially prone to forming the amyloid deposits.

In people, mutations in this gene probably bring on Alzheimer’s by making brain cells overproduce this version of beta amyloid, which in turn encourages the formation of the protein deposits, the researchers said. The work was led by Karen Duff of the University of South Florida in Tampa with colleagues there and at the Mayo Clinic Jacksonville in Florida.

Prior work suggests that mutations in another gene that causes Alzheimer’s in people, called APP, also leads to an overproduction of the same form of beta amyloid. So an excess of this version appears to be crucial for producing the inherited disease and maybe the non-inherited form as well, Duff said.

Another study, scheduled for publication in the journal Neuron, reports similar findings in mice.