Further findings over Alzheimer’s

Arare genetic resilience to Alzheimer’s disease has been identified in a second patient, a new study suggests.

Researchers have found a patient with a genetic predisposition for developing early-onset Alzheimer’s who remained cognitively intact until his late 60s.

According to the study, a series of tests and analyses revealed a new genetic variant (differences in DNA between people) that provides protection from the disease.

The variant occurs in a different gene than in a case from the same family reported in 2019, but points to a common disease pathway, the study suggests.

The findings also identify a region of the brain that may provide an ideal treatment target in the future, according to an international team led by investigators from two Mass General Brigham hospitals in the US – Massachusetts General Hospital (MGH) and Mass Eye and Ear.

Co-senior author Joseph Arboleda-Velasquez, an associate scientist at Mass Eye and Ear, said: “The genetic variant we have identified points to a pathway that can produce extreme resilience and protection against Alzheimer’s disease symptoms.

“These are the kinds of insights we cannot gain without patients.”

The case that caught the investigators’ attention involved a family member of the world’s largest-known family and relations with a genetic variant called the “Paisa” mutation.

Carriers of this variant usually develop mild cognitive impairment at an average age of 44, dementia at 49, and die from complications of the conditions in their 60s.

Francisco Lopera, director of the Neuroscience Group of Antioquia in

Medellin, Colombia, a cofirst author of the Nature Medicine paper, is the neurologist who discovered this family and has been following them for the last 30 years.

The researchers had previously studied a woman from the family who remained unimpaired until her 70s and whose case was reported in 2019.

In the new study they describe a case of a male carrier of the 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, researchers say.