Taking aim at plaques

Some of the new Alzheimer's treatments in development target microscopic clumps of the protein beta-amyloid (plaques). Plaques are a characteristic sign of Alzheimer's disease.

Strategies aimed at beta-amyloid include:

• Recruiting the immune system. Several drugs — known as monoclonal antibodies — may prevent beta-amyloid from clumping into plaques or remove beta-amyloid plaques that have formed and help the body clear the beta-amyloid from the brain. Monoclonal antibodies mimic the antibodies your body naturally produces as part of your immune system's response to foreign invaders or vaccines.

  In June 2021, the Food and Drug Administration (FDA) approved aducanumab for the treatment of some cases of Alzheimer's disease. This is the first drug approved in the United States to treat the underlying cause of Alzheimer's by targeting and removing amyloid plaques in the brain. The FDA approved the drug on the condition that further studies be conducted to confirm the drug's benefit. Experts also need to identify which patients may benefit from the drug.

  The monoclonal antibody lecanemab shows promise in removing amyloid and has moved into phase 3 clinical trials.

  Donanemab is another monoclonal antibody that showed promise in phase 2 trials and is moving into phase 3.

  In studies, the monoclonal antibody solanezumab did not demonstrate any benefit for individuals with mild or moderate Alzheimer's disease. It's possible that solanezumab may be more effective when given earlier in the course of the disease. The drug seemed safe in recent studies, and solanezumab continues to be evaluated in the preclinical stage of the disease.

• Preventing destruction. A drug initially developed as a possible cancer treatment — saracatinib — is now being tested in Alzheimer's disease.

  In mice, the drug turned off a protein that allowed synapses to start working again, and the animals experienced a reversal of some memory loss. Human trials for saracatinib as a possible Alzheimer's disease treatment are now underway.

• Production blockers. These therapies may reduce the amount of beta-amyloid formed in the brain. Research has shown that beta-amyloid is produced from a "parent protein" in two steps performed by different enzymes.

  Several experimental drugs aim to block the activity of these enzymes. They're known as beta- and gamma-secretase inhibitors. Recent studies showed that the beta-secretase inhibitors did not slow down cognitive decline and were associated with significant side effects in those with mild or moderate Alzheimer's, which has decreased enthusiasm for this mechanism of drug.