Researchers have made another breakthrough in their effort to help Alzheimer’s patients, as Boston scientists on Monday reported they have found a new genetic variant that protects against Alzheimer’s disease symptoms.
Meanwhile, other researchers in the city recently discovered how the FDA-approved Alzheimer’s drug lecanemab slows cognitive decline, and the FDA gave the green light for a drug to treat agitation symptoms that are associated with dementia.
Mass General Brigham investigators on Monday said they identified what’s causing Alzheimer’s, and also what protects against the disease — helping pave the way for future treatments.
The researchers studied a patient with a genetic predisposition for early-onset Alzheimer’s disease who remained cognitively intact more than two decades beyond the expected age of memory impairment.
“The genetic variant we have identified points to a pathway that can produce extreme resilience and protection against Alzheimer’s disease symptoms,” said Joseph Arboleda-Velasquez, an associate scientist at Mass Eye and Ear.
The case that caught the investigators’ attention involved a family member with a genetic variant called the “Paisa” mutation. Carriers of this variant usually develop mild cognitive impairment at the age of 44, dementia at age 49, and die from complications of dementia in their 60s.
These investigators previously studied a woman from this family who remained unimpaired until her 70s. In this new study, the researchers reported on a male carrier of the Paisa mutation who remained cognitively intact until age 67.
He progressed to mild dementia at age 72 and died at 74 — decades after most people with the Paisa mutation typically do.
“The insights we are gaining from this second case may guide us on where in the brain we need to look to delay and stop disease progression and will help us form new hypotheses about the series of steps that may actually lead to Alzheimer’s dementia,” said Yakeel Quiroz, director of the Familial Dementia Neuroimaging Lab in the departments of Psychiatry and Neurology at Massachusetts General Hospital.
In other Alzheimer’s research, Brigham and Women’s Hospital researchers have revealed the structure of the therapeutic target of lecanemab, an FDA-approved drug for the treatment of Alzheimer’s.
“For the first time, we describe the structure of a special type of amyloid beta plaque protein associated with Alzheimer’s disease progression, revealing the identity of the enemy,” said Dennis Selkoe, co-director of the Ann Romney Center for Neurologic Diseases at the Brigham.
“These findings are extremely timely as we make key strides in developing treatments that can reduce cognitive decline,” Selkoe added.
Also, the FDA has OK’d the first drug to treat agitation that’s associated with dementia — Rexulti oral tablets.
Agitation can include symptoms ranging from pacing or restlessness to verbal and physical aggression.
Tiffany Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, said, “These symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression.”
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