Rare mutation delays onset of Alzheimer's disease

There is only one copy Apoe 3 The Christchurch variant is Dog 1 Retrospective data revealed autosomal dominant Alzheimer's disease.

During the career Dog 1 I also had a copy of the E280A. Apoe 3 In patients with the Christchurch mutation, the mean age at onset of cognitive impairment was 52 years (95% confidence interval: 51 to 58 years), compared with 47 years (95% confidence interval: 47 to 49 years) in a matched group of patients without the Christchurch mutation, said Dr. Yakiel Quiroz of Massachusetts General Hospital in Boston and colleagues. New England Journal of Medicine.

The mean age at dementia onset in Christchurch carriers was 54 years (95% CI 49-57) compared with 50 years (95% CI 48-51) in non-carriers.

Career Dog 1 E280A is predisposed to developing autosomal dominant Alzheimer's disease and belongs to a large family from the Colombian state of Antioquia. The family is made up of approximately 6,000 relatives, of which approximately 1,200 Dog 1 The average age of onset of Alzheimer's disease in these patients is Dog 1 I have 45 career years.

In 2019, Quiros and colleagues Dog 1 In E280A mutation carriers Part 2 of Apoe 3 The Christchurch variant did not show cognitive impairment for nearly 30 years after the predicted age of clinical onset. Another variant In Colombian relatives, it appears to have a delayed effect on cognitive symptoms.

The study also reports on 27 other families who carried just one copy of the Christchurch variant.

Quiroz said the data could have implications for Alzheimer's drug development. “As clinicians, we are extremely encouraged by the findings of this study, which suggest that we may be able to slow cognitive decline and dementia in older adults,” he said in a statement.

“As neuroscientists, our findings Apoe This could lead to the discovery of a critical mutation in Alzheimer's disease, paving the way for innovative treatments for the disease. ApoeRelated Paths

“Genetic mutations Apoe “The gene locus is the most important determinant of Alzheimer's disease risk yet discovered,” said John Hardy, MD, PhD, of University College London. Accompanying editorial“Despite this, little is understood about its pathogenic role beyond the fact that genetic variants are closely associated with amyloid deposition.”

The most common defense genes are Apoe 2It affects about 10 percent of the general population, Hardy said. Apoe 2 Homozygotes: about 5 years Apoe 2 Heterozygote.

both Apoe 3 Christchurch homozygous and Apoe 2 Hardy noted that homozygosity is associated with type III hyperlipoproteinemia. “This observation suggests that Apoe “The variants disrupt interaction with the APOE receptor in a similar way, which as such may provide clues to the mechanism of both conditions,” he wrote.

Quiros and his coauthors evaluated data from 27 subjects. Apoe 3 The Christchurch variant is the most common in 1,077 cases. Dog 1 E280A carriers of Antiochian ancestry.Of the 27 participants, two underwent brain imaging and four underwent autopsy.

In two subjects who underwent brain imaging, PET scans showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease, and autopsy material showed that patients with the Christchurch variant had less vascular amyloid pathology, a greater amyloid plaque burden, and a relatively limited tau burden compared with other patients. Dog 1 E280A derivative carrier.

“PET imaging diagnosis, Apoe 3 Christchurch mutations are associated with limited tau pathology and relatively preserved glucose metabolism, suggesting a delayed clinical onset associated with this mutation. Apoe 3 “The Christchurch variant may be involved in mechanisms limiting tau pathology and neurodegeneration, even in the setting of high amyloid-β plaque burden,” Quiroz and his co-authors wrote.

The limitations of the study include: Apoe 3 Christchurch and Dog 1 The E280A variant increases uncertainty regarding the difference in point estimates between age at onset of mild cognitive impairment and dementia. Findings regarding the Christchurch variant in this Colombian cohort may not apply to people with sporadic Alzheimer's disease or other groups of people.