Doug Whitney May Have the Key to Aiding Alzheimer's

    In this NYTimes article, Doug Whitney has been the focus of research for 14 years due to the fact he doesn’t have Alzheimer's Disease. This wouldn’t be anything special except for the fact that he was expected to show symptoms in his 50s, but now he is 76 with no signs. His family has the rarest mutation called Presenilin 2, which is shown to cause early-onset Alzheimer’s disease and has been seen in the family with memory problems starting to show between the ages of 44 and 53. After a while without seeing any issues, Mr. Whitney decided to go through with genetic testing and was confirmed to have the mutation, but no symptoms, which led to further research.

Alzheimer's is seen by the abnormal accumulation of two proteins in the brain: amyloid, followed by tau. Amyloid starts to clump together years before symptoms, and tau forms tangles after the accumulation of amyloid. It was found that Mr. Whitney’s brain was full of amyloids, but didn’t have nearly as many tau, which suggested that his brain is resistant to tau aggregation and spreading. Looking at his DNA, researchers have discovered that there are a couple of variations that his relatives didn’t have that could be helping with the prevention of Alzheimer’s. It was found that he has an excess of heat shock proteins that help keep proteins from folding incorrectly. This excess may be the reason why there aren’t as many misfolded proteins, especially tau, in his brain, since it can prevent them from spreading. There are many theories on why this has happened, but it is still being tested to find that piece of the puzzle.

Alzheimer’s disease is a disease that has no cure and affects many people and their families. This research could be a big breakthrough for those people and give hope for a cure or at least assistance for those who have it. I believe that this research is extremely important, since I know people whose family has a history of diseases that cause brain deterioration, and this could help ease their worries. Even if this doesn’t lead to a cure, it’ll help guide our understanding of these issues and get us one step closer.

Deletion of the Abi3 Gene Can Increase the Development of Alzheimer’s Disease

In the article, “Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis,” a study was conducted to determine whether the loss of the gene Abi3 can increase the chances of developing Alzheimer’s disease (AD). The study, led by Hande Karahan and Jugnsu Kim, at the Indiana University School of Medicine discovered that the deletion of the gene mutation ABi3 decreases the amount of microglia found within the brain. Microglia cells are the predominant immune cells in the body, but when they are damaged it can cause a series of neurological diseases. They can play a role in brain infections and inflammation. To confirm their findings, they tested it using mouse models by removing the ABi3 gene in the mouses that had AD. 

Through the mouse models, they were able to see the increased levels of inflammation and dysfunctions relating to learning and memory deficits in the brain. Also, they saw the it had impaired the movement of the microglia cells. After examining the mouse models closely, they were able to come to the conclusion that the loss of the ABi3 gene can possibly be another factor in the risk of developing Alzheimer’s disease. 

https://www.sciencedaily.com/releases/2021/11/211106125841.htm 

https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABI3

New Cellular Defense Mechanism against Stress

     

     Scientists studying neuronal malfunctioning, long thought to be a result of a cell’s reaction to stress, may have unlocked a new understanding and even a treatment plan for the future. Science Daily explains that neurodegenerative diseases such as Alzheimer’s and Parkinson’s are caused in part by a cell’s reaction – or lack thereof – to stress. Scientists from Harvard and NYU have identified a protein modification that signals for the cell to begin protein synthesis, in turn strengthening and protecting the cell from attack.

     Oxidative attack – the focus of this research – is when cells are exposed to hazardous conditions (pollution, cigarette smoke, radiation). Exposure to these stimulates the stress response in cells to begin degradation of weak or damaged proteins. It is speculated that with less impaired proteins in the way, the cell can begin protein synthesis and restructure itself. Using this new research, scientists may be able to harness the removal of such proteins and one day focus on a treatment plan for neurodegenerative diseases. 

Location on Human Genome Now Associated With Memory

With a recent analysis of genomic data and memory test results of over 14,000 older adults a location of the human genome has been identified to relate to better memory performance which was not associated with brain performance before. The gene known as FASTKD2, located on chromosome 2, revealed that better episodic memory resulted from a G nucleotide rather than the common A nucleotide. This change known as a single nucleotide polymorphism was also connected to a larger hippocampus, a brain structure involved with storing and retrieving memory, and increased gray dense matter in the brain on magnetic resonance imaging scans.

Although, there is no claim that this is the gene which is solely responsible for memory but the hopes of this information is that the FASTKD2 gene could be targeted to help those with conditions such as Alzheimer's disease. A decline in memory and hippocampal atrophy are two of the main symptoms which are associated with Alzheimer's therefore the correction of those symptoms by targeting the FASTKD2 gene is where research is now heading.

This was especially interesting to me because it is a new, and genetic, solution to attempting to treat Alzheimer's. There have been a lot of suggestions of what can help prevent or prolong the effects of Alzheimer's but now with a new approach there is an attempt to help treat as well. I also just found it intriguing that memory could be found to be associated with a specific gene, although it is not a single gene responsible for memory.
Article
Related Article

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/