The man who is the protagonist of what researchers call “resilience” to Alzheimer’s it was part of a decades-long study involving 6,000 people living in Colombia who had a genetic mutation that causes the disease at a young age, more specifically in middle age.
With astonishment, researchers from two Mass General Brigham hospitals, Massachusetts General Hospital (MGH) and Mass Eye and Ear, reported the finding of a new case of a patient with a genetic predisposition to developing early-onset Alzheimer’s disease who remained cognitively intact until he is 67 years old.
The job was published this Monday in the magazine nature medicine and accounts for the second patient identified with the miraculous ability to defy the devastating gene for Alzheimer’s, a disease that could affect 78 million people by 2030.
The autosomal dominant Alzheimer’s disease (ADAD) is a rare inherited form of the disease, which is most commonly caused by specific mutations in the PSEN1 gene encoding the transmembrane protein presenilin 1. It is characterized by early onset cognitive impairment, such as deficits from memory, at a young age, typically at 40-50 years of age.
The previous case involved a woman who carried the E280A mutation in a gene called Presenilin 1 (PSEN1), which has been shown to cause early-onset Alzheimer’s disease.
“We identified a male carrier of the PSEN1 -E280A mutation who remained cognitively intact until he was 67 years old,” the study authors stated in the publication. He completed five years of formal education in his home country (Colombia) and worked until retirement at age 60. He was married and had two children. His first cognitive assessment at age 67 revealed limited verbal learning abilities and language difficulties in the context of functional independence. The patient was diagnosed with mild cognitive impairment, characterized by decreased short-term memory and verbal fluency at age 70.
At age 72, her language had deteriorated further, progressing to mild dementia. And as the researchers recorded, “the cognitive decline was preceded by an episode of septic shock related to a urinary tract infection.” “At age 73, she required assistance with basic and instrumental activities of daily living and met criteria for moderate dementia,” they recorded. She died at the age of 74 of aspiration pneumonia; Her relatives agreed to a brain donation for neuropathological study”.
As said, it is about second case of such resilience from a large family of more than 6,000 living members from Colombia, who did not develop mild cognitive problems nearly two decades after the typical age of onset. “The research uncovers a new molecular pathway that could be a therapeutic target to potentially increase resilience in all forms of Alzheimer’s disease,” explained Joseph F. Arboleda-Velásquez, from Harvard Medical School and one of the paper’s authors.
Francisco Lopera, MD, director of the Grupo de Neurociencias de Antioquia in Medellín, Colombia, is a co-author of this article and is the neurologist who discovered this family and followed its evolution over the past 30 years. This team of researchers had previously studied a woman from this family who remained intact until she was 70 years old and whose case was reported in 2019.
“Extraordinary cases like this illustrate how individuals and extended families with Alzheimer’s disease can help advance our understanding of the disease and open new avenues for discoverysaid co-lead author Yakeel T. Quiroz, PhD, a clinical neuropsychologist and neuroimaging researcher in the Familial Dementia Neuroimaging Laboratory in the Massachusetts General Hospital Departments of Psychiatry and Neurology.
While stressing: “The insights we are gaining from this second case may guide us as to where in the brain we should look to slow and stop the progression of the disease and help us form new hypotheses about the series of steps that can actually lead to Alzheimer’s dementia.
For decades Lopera has been treating and following this extended family, many of whose members carry a tragically unfortunate mutation in a gene called presenilin 1. The mutation is rare and its effects are aggressive and predictable.
By their late 20s, people who carry the mutation have their brains clogged with the amyloid plaques characteristic of Alzheimer’s disease. In your mid-30s, tangles of a different protein associated with Alzheimer’s, known as tau, appear. People who carry this gene begin to experience the first signs of cognitive problems around age 44, and by age 49, they have full-blown dementia. They usually die at age 60. In total, the scientists found 1,200 people carrying this genetic “bomb”.
But in 2019, researchers discovered a single patient – Aliria Rosa Piedrahita de Villegas – who seemed to have fended off fate: Her memory didn’t begin to decline until she was 70. Scientists discovered a genetic mutation that protected her from it, dubbed christchurch. And while her brain was clogged with the amyloid plaques characteristic of Alzheimer’s disease, it was relatively free of the tau tangles that are also associated with the disease.
The researchers believe the two patients are revealing a New way to treat Alzheimer’s. The two genes that are mutated disrupt a molecular cascade of events required for tau to aggregate in the brain.
Hypotheses that a drug might protect the entorhinal cortices of other patients require further investigation. But animal studies are already underway, Arboleda-Velásquez said. Members of the group are injecting the mutant form of the gene into the same part of the brain in mice that are predisposed to Alzheimer’s-like disease to see if it is protective.
For Dr. Eric Reiman, a member of the research team, executive director of the Banner Alzheimer’s Institute in Phoenix, and adviser to several pharmaceutical companies, “the future may involve a combination of therapies; the hope is to prevent the buildup of amyloid and tau and delay Alzheimer’s in those susceptible so long that it is no longer a problem in their lives.”
Keep reading
