Can the Christchurch (ApoE3) Mutation Halt Alzheimer’s Disease?

A team of researchers led by Yakeel Quiroz, Joseph Arboleda-Velasquez, Francisco Lopera, and Eric Reiman describe the case of a Colombian woman who inherited the autosomal-dominant E280A mutation in presenilin 1 but stayed cognitively well for decades past this mutation’s typical age of disease onset. While she had fewer neural tangles in her brain than is typical for Alzheimer's patients, by the time she hit her 40s she did have the same unusually high level of brain amyloid-beta deposits as her E280A peers. Such deposits are a key signature of Alzheimer's. The researchers believe the answer is a rare mutation in ApoE3 that disrupts the protein’s ability to bind lipoprotein receptors and other proteoglycans. Not only did she carry the Christchurch mutation, but she had two of them. No protection against dementia was linked to only one Christchurch mutation. But as this woman's case suggests, having two such mutations did seem to throw up a shield against Alzheimer's, preserving her ability to remember things and think clearly for a few decades, long after her E280A peers had started experiencing cognitive decline. In theory, the incredibly rare experience of this one woman in Colombia could ultimately have profound ramifications for Alzheimer's patients around the world, if "new drugs that mimic the effect of the mutation" could be developed, said Arboleda-Velasquez. Rather than stopping Alzheimer's from developing, such drugs would prevent Alzheimer's from causing dementia.




Article: https://www.alzforum.org/news/research-news/can-apoe-mutation-halt-alzheimers-disease

Related Article: https://www.usnews.com/news/health-news/articles/2019-11-04/a-gene-kept-one-woman-from-developing-alzheimers-could-it-help-others

Gene Mutation Could Help Prevent Dementia in Alzheimer's Patients

Alzheimer's is neurodegenerative disease that leads to cell and tissue death to the brain. Over time the brain shrinks and almost all functions of the brain are affected. The cell death and tissue loss seems to be due to plaque and nerve tangles in the brain. Alzheimer's is the most common cause for dementia, which has a range of symptoms including memory loss, lower performance of daily activities, and issues communication. One woman was found to have a gene that prevented dementia for years even though her brain was affected with Alzheimer's. This woman was part of a population that had an increased risk of early-onset Alzheimer's because she carried the E280A mutation of a gene called Presenilin 1, yet she did not develop dementia like the rest of the people carrying this mutation. An analysis showed that Alzheimer's had affected her brain, yet dementia didn't start to set in until her 70s. An in depth genetic analysis was done and revealed that she had another mutation called the "Christchurch" mutation in the APOE3 gene. Only about 6% of the population with the E280A mutation, also had the "Christchurch" mutation. The difference, though, was that she had a double copy of this mutation compared to the others who only had one copy. This double copy of the mutation seemed to be some type of genetic barrier against dementia by slowing down its development, even if the brain has already been affected by Alzheimer's. More research needs to be done to see how this mutation actually stunts the development of dementia for a while, but this mutation could be a key for treating Alzheimer's patients.

Alzheimer's affects a lot of people, especially people that are older. Once it is diagnosed there isn't a lot that can be done to slow down or stop the development of dementia. This gene mutation could be the key for developing a treatment for people that have been diagnosed with Alzheimer's, and slow down the development of dementia.

Links:

https://www.usnews.com/news/health-news/articles/2019-11-04/a-gene-kept-one-woman-from-developing-alzheimers-could-it-help-others

Related Article:

https://www.alz.org/alzheimers-dementia/what-is-alzheimers/brain_tour_part_2

The Two-Faced Alzheimer’s Gene

         A team of researchers at Harvard University set out to understand gene apolipoprotein E or more commonly APOE and how it plays a role in Alzheimer’s disease. Currently this neurodegenerative disease is the 6^th leading cause of death in the United States. It is known that those carrying a specific version of the APOE called APOE4 increases the risk of developing late onset Alzheimer’s disease. The APOE gene is responsible for making proteins that transport cholesterol. Using mice with an “Alzheimer’s like disease” they injected each one with APOE2, APOE3 or APOE4. Mice that were injected with APOE4 had a 10% increase in plaque formation and amyloid beta. These plaque and amyloid beta tangles are a key suspected to play a key role in Alzheimer’s disease progression. Mice injected with APOE2 on the other hand were found to have a 10% decrease in these plaque formations and tangles. This research shows that while APOE4 decreases the number of synapse connections APOE2 protects them, mice injected with APOE3 were found to have no significant difference in Alzheimer’s symptoms. The findings of this study are exciting when thinking of the possibility of gene therapy. Currently about 14% of the population carries the APOE2 version of APOE while 7% of the population carries APOE4. The team now wants to look at ways to decreasing or inhibiting APOE2 and increase APOE2.
 

Link:

https://www.sciencenews.org/blog/scicurious/gene-boosts-alzheimer%E2%80%99s-risk-might-protect-against-it-too

Related Links:

http://www.medpagetoday.com/Neurology/AlzheimersDisease/43056

http://www.alz.org/