- Some people are genetically predisposed to developing early-onset Alzheimer’s disease before the age of 65.
- Researchers at Mass General Brigham have discovered a genetic variant that could help protect people with a variant in a different gene that predisposes them to developing early-stage Alzheimer’s disease.
- This could offer potential for new therapeutic targets for the early treatment of Alzheimer’s disease.
About
Although most people do not develop Alzheimer’s disease until age 65, it can sometimes appear earlier, even as early as your 30s. Alzheimer’s disease before the age of 65 is called young-onset Alzheimer’s disease.
Researchers believe that most early cases of Alzheimer’s are caused by
Now, researchers at Mass General Brigham have discovered a
The study was recently published in The New England Journal of Medicine.
For this study, the researchers focused on two specific genetic mutations.
The first is called the Paisa mutation (Presenilin-1 E280A), known to be present in a large family in Colombia.
Previous research shows that people with the Paisa mutation are in a difficult situation.
The second genetic variant examined by the researchers in this study concerns
THE
Another study in January 2024 found that the Christchurch mutation could help protect the brain against clumps formed by excessive amounts of the protein.
Scientists analyzed the genetic data of 1,077 descendants of the Colombian family carrying the Paisa mutation.
They identified 27 family members who carried both the Paisa mutation and one copy of the Christchurch variant. On average, these family members did not start showing signs of cognitive impairment until they were 52 years old, compared with family members who did not have the Christchurch variant and had symptoms at age 47.
Researchers also reported that family members carrying at least one copy of the Christchurch variant showed signs of dementia four years later than those who did not carry the variant.
“As a clinician, I am very encouraged by our results, as they suggest the potential for delaying cognitive decline and dementia in older adults,” says Yakeel T. Quiroz, PhD, clinical neuropsychologist and neuroimaging researcher and director of the familial dementia neuroimaging laboratory. in the Departments of Psychiatry and Neurology at Massachusetts General Hospital and co-first author of this study.
“Now we must harness this new knowledge to develop effective treatments for dementia prevention. As a neuroscientist, I am excited by our findings because they highlight the complex relationship between APOE and a deterministic mutation in Alzheimer’s disease, potentially paving the way for innovative therapeutic approaches for Alzheimer’s disease, including targeting APOE-related pathways.
—Yakeel T. Quiroz, PhD
“As a next step, we are currently focusing on improving our understanding of the brain resilience of other family members carrying a copy of the Christchurch variant,” Quiroz continues.
“This involves performing structural and functional MRI scans and cognitive assessments, as well as analyzing blood samples to assess their protein and biomarker profiles. The unwavering commitment to research demonstrated by our Colombian patients with autosomal dominant Alzheimer’s disease and their families was essential in making this study possible and allowing us to continue working toward interventions against this devastating disease,” explains- he.
After reviewing this study, Karen D. Sullivan, PhD, ABPP, board-certified neuropsychologist, owner of I CARE FOR YOUR BRAIN and Reid Healthcare Transformation Fellow at FirstHealth of the Carolinas in Pinehurst, North Carolina, said: Medical news today that this is an exciting study because it adds new evidence on protective mechanisms in early-onset Alzheimer’s disease.
“This opens the door to new drug targets in populations with the highest genetic risk of this devastating disease,” Sullivan explained. “It is a new discovery to see an increased protection mechanism linked to APOE rather than an increased risk.
“We think about 60 to 80 percent of Alzheimer’s cases are linked to genetic variants,” she continued. “There will be no cure for Alzheimer’s disease without deciphering the genetic code.We need larger groups of participants and people with other subtypes of Alzheimer’s disease, including the much more common and older variant, to see if the protective effects of the Christchurch variant are also stake. ”
MNT also spoke with Manisha Parulekar, MD, FACP, AGSF, CMD, director of the Division of Geriatrics at Hackensack University Medical Center and co-director of the Center for Memory Loss and Brain Health at Hackensack University Medical Center Hackensack University in New Jersey, about this study.
“We continue to learn more about the pathophysiology and risk factors of Alzheimer’s disease and early-onset Alzheimer’s disease. Having a family member with an early-onset illness is stressful for the individual. Having access to information about protective genetic markers will be beneficial in navigating these complex conversations.
—Manisha Parulekar, MD
“Alzheimer’s disease affects a large population worldwide,” she continued. “Knowledge of the details of various genetic variants is helpful in implementing care plans for patients and their family members. Increasing access and education about the benefits of understanding genetic variants can allow us to support individuals and families with this disease with comprehensive care plans in a timely manner.”