NIH-funded study identifies gene variant as potential drug target
Defying the odds, an individual at high risk for early-onset Alzheimer’s disease remained dementia-free for many years beyond what was anticipated. A study funded in part by the National Institute on Aging (NIA), part of the National Institutes of Health, led researchers to suggest that a gene variant may be the key, perhaps providing a new direction toward developing a treatment.
The research focused on the case of a woman who carried a gene mutation known to cause early-onset Alzheimer’s. However, she did not develop signs of the disease until her seventies, nearly three decades after her expected age of onset. The researchers suspect that she may have been protected because in addition to the gene mutation causing early-onset Alzheimer’s in her family, she also had two copies of the APOE3 Christchurch (APOE3ch) gene variant. Findings of this case study as published in Nature Medicine suggest that two copies of the APOE3ch variant, named after Christchurch, New Zealand where it was first identified, may protect against Alzheimer’s.
“Sometimes close analysis of a single case can lead to discovery that could have broad implications for the field,” said NIA Director Richard J. Hodes, M.D. “We are encouraged that as part of our wide array of studies, this research in the unique genetic makeup of an exceptional individual can reveal helpful information.”
Early-onset Alzheimer’s disease is rare, representing less than 10% of all people who have Alzheimer’s. It typically occurs between a person’s 30s to mid-60s. Risk for both early- and late-onset Alzheimer’s disease is affected by genetic factors.
For the study, researchers led by investigators at Massachusetts General Hospital, Boston, in collaboration with the University of Antioquia, Medellin, Colombia, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, and Banner Alzheimer’s Institute, Phoenix, looked at genetic data from a Colombian family with more than 6,000 living members. Family members who carry a rare gene mutation called Presenilin 1 (PSEN1) E280A, have a 99.9% risk of developing early-onset Alzheimer’s disease.
The researchers confirmed that the woman in this case carried the PSEN1 E280A mutation, which caused early-onset Alzheimer’s in her other family members. However, she also had two copies of the APOE3ch gene variant, while no other affected family member carried two copies of this variant. Affected family members develop Alzheimer’s in their 40s, but she remained disease free until her 70s. Imaging tests showed that the woman had only minor neurodegeneration. She did have large amounts of amyloid protein deposits, a hallmark of Alzheimer’s disease, in her brain. But the amount of tau tangles, another hallmark of the disease, and the one more correlated with how thinking and memory are affected, was relatively low.
Experiments as part of the study showed that the APOE3ch variant may reduce the ability of APOE to bind to certain sugars called heparan sulphate proteoglycans (HSPG). APOE binding to HSPG has been implicated as one mechanism that may contribute to the amyloid and tau protein deposits that destroy the brain. The research suggests that a drug or gene therapy that could reduce APOE and HSPG binding has the potential to be a new way to treat or prevent Alzheimer’s disease.
The Latest on: Alzheimer’s
via Google News
The Latest on: Alzheimer’s
- Time Warp Comics Teams Up With Local Artist to Help End Alzheimer’son August 5, 2022 at 4:00 am
And on Tuesday, August 9, the real-life heroes are Wayne Winsett’s Time Warp Comics up in Boulder and Denver artist Joe Rollman, who are coming together to support fellow comic-book lover Matt Henry ...
- How Microglia Contribute to the Slowdown of Neuron Activity in Alzheimer’s Diseaseon August 5, 2022 at 2:22 am
The reduced firing of some neurons in the brain is a characteristic of Alzheimer's disease and a new study details how microglia contribute to the reduction of neural activity.
- From buzzy biomarkers to learning from failure: 3 takeaways from the Alzheimer’s Association International Conferenceon August 5, 2022 at 1:30 am
From exploring new ways to spot the disease to rethinking how to treat Alzheimer’s, there was plenty to absorb at this week’s Alzheimer’s Association International Conference.
- Latest data on lecanemab presented at Alzheimer's Association International Conference (AAIC): BioArcticon August 4, 2022 at 11:17 pm
BioArctic AB's (publ) (Nasdaq Stockholm: BIOA B) partner Eisai presented new data for lecanemab (BAN2401), an investigational anti-amyloid beta (Aβ) protofibril antibody for the treatment of mild ...
- Study of Alzheimer's risk gene reveals potentially reversible mechanismon August 4, 2022 at 8:20 pm
MIT scientists have uncovered a mechanism for how a common genetic risk factor for Alzheimer’s contributes to the disease. It centers on lipid metabolism, and early investigations suggest it could ...
- Cold sores and shingles may be linked to Alzheimer’s, new research indicateson August 4, 2022 at 2:57 pm
Could cold sores plus shingles lead to? New research from Tufts and Oxford universities adds to the growing evidence that they might — and how. And the implication ...
- How microglia contribute to Alzheimer's diseaseon August 4, 2022 at 9:40 am
One of the hallmarks of Alzheimer's disease is a reduction in the firing of some neurons in the brain, which contributes to the cognitive decline that patients experience. A new study from MIT shows ...
- Advancing Alzheimer’s researchon August 3, 2022 at 12:01 pm
The new Delaware Center for Cognitive Aging Research at UD, funded by an initial $150,000 investment from the College of Health Sciences Dean’s Office, aims to stimulate new NIH-funded research and ...
- Blood Test Spots Signs of Alzheimer's Years Before Symptoms Appear: Scientistson August 2, 2022 at 11:59 am
Scientists have created a sensor that can detect signs of the condition years before they first manifest themselves.
- As new Alzheimer’s drugs have failed, scientists are shifting focus to other potential causeson August 2, 2022 at 9:05 am
Toxic plaque buildup in the brain may play a role in the disease, but in the search for effective treatments, researchers are looking to other potential causes.
via Bing News