PSEN2 Mutations Double Trouble for Alzheimer’s Patients
The rarest forms of Alzheimer’s disease stem not from lifestyle or age but from genetic mutations passed down through families. For these individuals, the onset of cognitive decline can start earlier and progress more rapidly, robbing them of cherished memories and the ability to navigate everyday activities.
Now, researchers have uncovered a significant piece of the puzzle regarding one particular genetic culprit: PSEN2. Their findings, focusing on familial Alzheimer’s disease, reveal that these mutations not only increase the production of harmful amyloid plaques in the brain, but also disrupt crucial waste disposal processes within brain cells.
amyloid plaques, clumps of protein fragments that hinder brain function, are a hallmark of Alzheimer’s disease. These plaques form when a protein called APP is cut by an enzyme complex called γ-secretase.
WhileThe γ-secretase
complex exists in two versions, one containing PSEN1 and another containing PSEN2, the specific role of PSEN2 has been a mystery. Until now.
This latest research sheds light on the dual impact of PSEN2 mutations.
“PSEN2 mutations have a double impact,” explains first author Anika Perdok. “They not only cause toxic amyloid plaques, but also disrupt the recycling processes in brain cells. This amplifies damage to brain connections and accelerates cognitive decline.”
Prof. Annaert’s team highlights that the recycling system within brain cells, responsible for clearing out waste and reusing essential components, is severely impacted by these mutations.
This overload leads to a build-up of harmful substances, damaging critical connections between nerve cells and interfering with their ability to communicate.
The consequences are devastating. Memory fades, learning becomes difficult, and everyday tasks become overwhelming.
New Hope for Treatment
Though the findings paint a stark picture, Professor Wim Annaert sees a glimmer of hope.
“Now that we better understand how PSEN2 mutations contribute to Alzheimer’s, we can think more specifically about possible treatments,” he says.
This newfound knowledge opens up exciting possibilities for targeted therapies that could slow the progression of this devastating disease.
“Therapies that restore waste processing in cells or improve the function of γ-secretase could help to slow the disease process in familial Alzheimer’s,” Prof. Annaert suggests.
This breakthrough emphasizes the power of scientific investigation in unraveling the complexities of neurological disorders. The hope is that these findings will pave the way for new treatments, offering brighter futures for those battling familial Alzheimer’s disease.
How do PSEN2 mutations contribute to the worsening of Alzheimer’s disease?
## PSEN2 Mutations Double Trouble for Alzheimer’s Patients
**(Host):** Joining us today is Dr. [Guest Name], a leading researcher in Alzheimer’s disease. Dr. [Guest Name], thanks for being here.
**(Dr. [Guest Name]):** It’s my pleasure to be here.
**(Host):** Dr.
|[Guest Name], your new research sheds light on the role of PSEN2 mutations in familial Alzheimer’s disease. Can you explain what makes these mutations so troubling?**
**(Dr. [Guest Name]):** Absolutely.
Familial Alzheimer’s disease (FAD), unlike the more common late-onset form, is caused by inherited gene mutations, which can lead to earlier onset and faster progression of the disease. Our research focuses on PSEN2, one of these genes. We’ve discovered that PSEN2 mutations are not only responsible for increasing the production of amyloid plaques, those notorious clumps of protein that damage brain cells. But they also disrupt a crucial system within brain cells responsible for clearing away waste.
**(Host):** So it’s a double whammy?
**(Dr. [Guest Name]):** Precisely.
Think of it like this: amyloid plaques are like trash piling up in the brain, and PSEN2 mutations not only create more trash but also break the garbage disposal system, making the problem worse.
**(Host):** This is groundbreaking! What are the implications of this discovery for developing new treatments?
**(Dr. [Guest Name]):** It opens up exciting new possibilities.
Our findings point to PSEN2 as a key target for potential therapies. By finding ways to either prevent the harmful effects of PSEN2 mutations or boost the brain’s own waste disposal mechanisms, we could significantly slow down, or even prevent, the progression of FAD.
**(Host):**
Thank you so much, Dr.
[Guest Name], for sharing this important information.
This has been a fascinating glimpse into the complexities of Alzheimer’s disease.
**(Dr. [Guest Name]):** My pleasure. Thanks for having me.
**[1](https://medicalxpress.com/news/2024-12-genetic-roots-rare-mutations-alzheimer.html)**
