Understanding Alzheimer’s: Study gives insights into how disease kills brain cells

Exactly how Alzheimer’s disease kills brain cells is still somewhat of a mystery, but University of Michigan researchers have uncovered a clue that supports the idea that small proteins prick holes into neurons.

The team also found that a certain size range of clumps of these proteins are particularly toxic to cells, while smaller and larger aggregates of the protein appear to be benign.

The findings, which appear in the journal PLOS ONE, add important detail to the knowledge base regarding this disease that affects 5.4 million Americans in 2012 but remains incurable and largely untreatable. The results could potentially help pharmaceutical researchers target drugs to the right disease mechanisms.

Small proteins called amyloid-beta peptides are the prime suspect for causing cell death in Alzheimer’s. They make up most of the senile plaque fibers found in the brains of autopsied patients. Researchers offer several hypotheses for how the peptides might cause the disease. They blame inflammation, oxidative stress or an imbalance of calcium ions possibly caused by holes in the cell membranes.

The U-M findings strongly support the idea that amyloid peptides damage the membrane around nerve cells and lead to uncontrolled movement of calcium ions into them. Calcium signaling is an important way that cells communicate and healthy cells regulate its flow precisely. The toxic mechanism implicated in the new study could act on its own or together with the other proposed courses and ultimately lead to a loss of brain cells in patients, the researchers say.