Education may be protective for people with gene for familial early onset Alzheimer's
August 5, 2020
Science Daily/American Academy of Neurology
Even for people who carry the gene for early onset Alzheimer's disease, more years of education may slow the development of beta-amyloid plaques in the brain that are associated with the disease, according to a new study published in the August 5, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.
About 1-6% of people with Alzheimer's disease have rare genes that cause the disease in everyone who has them. This is called familial Alzheimer's disease. It leads to an early onset of the disease, when people are in their 30s to 50s.
"Because we've assumed that the effects of these genes can't be changed, very little research has been done on whether we can modify the trajectory of the disease," said study author Sylvia Villeneuve, PhD, of the McGill University in Montreal, Canada. "It's exciting to see that education may play a role in delaying the start of this devastating disease, which affects people during the prime of life."
Most people diagnosed with Alzheimer's have the sporadic form of the disease, which is thought to be caused by a combination of both environmental and genetic factors, including a gene variant called APOE ?4, or apolipoprotein E ?4. Having this gene variant is known to increase the development of amyloid plaques in the brain, even though it does not guarantee that the person will develop symptoms of Alzheimer's disease.
The study involved two groups: one group of 106 people with an average age of 67 who had a parent diagnosed with the sporadic form of Alzheimer's disease, of whom 39% had the APOE ?4 gene variant; and another group of 117 people with an average age of 35 who had the gene mutations linked to familial early onset Alzheimer's disease, of whom 31% also had the APOE ?4 gene variant. Each group had an average 15 years of education. None of the participants showed symptoms of the disease at the start of the study.
Participants had brain scans to determine levels of amyloid plaques.
Researchers found that in the people with familial early onset Alzheimer's, increasing levels of education were associated with lower levels of amyloid plaques in the brain. The strength of the association between education and plaque levels was similar to the strength of this same association in people at risk of sporadic Alzheimer's disease.
In both groups, people with less than 10 years of education had about twice the amount of amyloid plaques when compared to people with more than 16 years of education.
"While it has been believed that people with familial Alzheimer's disease, with its strong genetic causes, may have few ways to slow development of the disease, our study shows that education may be somewhat protective, perhaps promoting brain resistance against these plaques, just as it has been shown to be in people with unknown causes of the disease," said Villeneuve.
A limitation of the study was that most participants were white, so results may not be the same for all people. Also, the quality of education may be affected by other factors like socioeconomic status, so future studies should look more closely at other factors in addition to years of education to determine whether other environmental factors may be at play to explain these study results.
https://www.sciencedaily.com/releases/2020/08/200805160829.htm
Possible Alzheimer's breakthrough suggested
January 22, 2020
Science Daily/Case Western Reserve University
Researchers at the Case Western University School of Medicine say they have identified a previously unknown gene and associated protein which could potentially be suppressed to slow the advance of Alzheimer's disease.
"Based on the data we have, this protein can be an unrecognized new risk factor for Alzheimer's disease (AD)," said Xinglong Wang, an associate professor of pathology at the School of Medicine. "We also see this as a potential novel therapeutic target for this devastating disease."
Wang said proving the latter assertion, which has not yet been tested in humans, would require additional research to corroborate the function of the protein they have dubbed "aggregatin." Eventually, that would someday mean clinical trials with Alzheimer's patients, he said.
"This protein characteristically accumulates, or aggregates, within the center of plaque in AD patients, like the yolk of an egg -- which is part of the reason we named it "aggregatin," Wang said.
A research team led by Wang and Xiaofeng Zhu, a professor of Population and Quantitative Health Sciences at the School of Medicine, has filed for a patent through the university's Office of Research and Technology Management for "novel Alzheimer's disease treatments and diagnosis based on this and related study," Wang said.
"We're very excited about this because our study is likely the first systematic work combining the identification from a genome-wide association study of high dimensional brain-imaging data and experimental validation so perfectly in Alzheimer's disease," Zhu said.
Their research was published this month by the scientific journal Nature Communications and supported by grants from the National Institutes of Health (NIH) and the Alzheimer's Association. Genomic and brain imaging data was obtained from the Alzheimer's Disease Neuroimaging Initiative, which is supported by the NIH.
Alzheimer's Disease affects millions
More than 5.7 million Americans have Alzheimer's disease, which is the primary cause of dementia and sixth-leading cause of death in the United States. That population is predicted to reach 14 million by the year 2050, according to the Alzheimer's Association.
The relationship between Alzheimer's (and subsequent brain atrophy) and amyloid plaques -- the hard accumulations of beta amyloid proteins that clump together between the nerve cells (neurons) in the brains of Alzheimer's patients -- has been well-established among researchers.
Less understood is precisely how that amyloid-beta actually leads to plaque formation -- and where this new work appears to have broken new ground, Wang said.
Further, while there has been much research into what genes might influence whether or not someone gets Alzheimer's, there is less understanding of genes that might be linked to the progression of the disease, meaning the formation of plaque and subsequent atrophy in the brain.
The role of 'aggregatin' protein
In the new work, the researchers began by correlating roughly a million genetic markers (called single-nucleotide polymorphisms, or SNPs) with brain images. They were able to identify a specific SNP in the FAM222, a gene linked to different patterns of regional brain atrophy.
Further experiments then suggested that the protein encoded by gene FAM222A is not only associated with AD patient-related beta-amyloid plaques and regional brain atrophy, but that "aggregatin" attaches to amyloid beta peptide -- the major component of plaque and facilitates the plaque formation.
So when researchers injected mouse models with the "aggregatin" protein (made from the FAM222A gene), plaque (amyloid deposits) formation accelerated in the brain, resulting in more neuroinflammation and cognitive dysfunction. This happened, they report, because the protein was found to bind directly the amyloid beta peptide, thus facilitating the aggregation and placque formation, Wang said.
Conversely, when they suppressed the protein, the plaques were reduced and neuroinflammation and cognitive impairment alleviated.
Their findings indicate that reducing levels of this protein and inhibition of its interaction with amyloid beta peptide could potentially be therapeutic -- not necessarily to prevent Alzheimer's but to slow its progression.
https://www.sciencedaily.com/releases/2020/01/200122080532.htm