As research into Alzheimer’s advances, scientists are shifting their focus from beta-amyloid accumulation to inflammation as a main driver of the disease. In a new study, researchers at the University of California, Irvine discovered that a protein known as TOM-1 plays a role in inflammation associated with Alzheimer’s disease.
“Scientists have known for a long time that inflammation is a driver of Alzheimer’s disease, but inflammation is complex and involves many factors,” Frank LaFerla, Dean of the School of Biological Sciences at the University of California, said in a press release. “That’s why we decided to look at TOM-1.”
TOM-1 and Inflammation
In the study, the researchers honed in on TOM-1’s link to inflammation in the brain.
“We were interested in TOM-1 because its levels are low in the Alzheimer’s brain and in the brains of Alzheimer’s rodent models,” Alessandra Martini, a postdoctoral researcher and author of the study, said in the press release. “However, its specific role in the disease has largely been unexplored.”
The study found that when TOM-1 levels were decreased in rodents, the animals experienced a rise in Alzheimer’s pathology—such as an increase in beta-amyloid buildup, inflammation and cognitive impairment—while boosting TOM-1 levels actually reversed these negative effects.
“[Reducing TOM1] worsens inflammation, impairs microglial phagocytosis, and significantly exacerbates amyloid deposition,” the authors wrote in the study. “Conversely, restoration of TOM1 reverses these effects and reduces amyloid-beta pathology. These results highlight the importance of endosomal adaptors and their interaction with inflammatory receptors in the pathogenesis of Alzheimer’s disease.”
Inflammation’s Role in Alzheimer’s
Brain inflammation, or neuroinflammation, can be a complicated topic. In many ways, inflammation works as a good force that helps clean the brain. Microglia, cells involved in the central nervous system’s immune response, scavenge and clear damaging elements like toxic proteins from the brain. They also release cytokines, pro-inflammatory molecules. In Alzheimer’s, however, this inflammatory response is over-activated and can become harmful.
“Inflammation is normally a ‘good guy.’ It clears infections and helps heal wounds, for example,” Linda Van Eldik, director of the Sanders-Brown Center on Aging at the University of Kentucky, told Being Patient in a past interview. “But in Alzheimer’s disease, the inflammation somehow gets out of whack. It gets too strong and sustains for too long—it’s now turned into a ‘bad guy,’ destroying the neurons that carry signals from one part of the brain to the next.”
While most Alzheimer’s drugs in development have focused on reducing beta-amyloid, more researchers are beginning to design therapeutic interventions that can fight inflammation.
The researchers of the latest study believe that TOM-1 may hold some answers to stopping inflammation as researchers continue to search for new therapeutic routes.
“You can think of TOM-1 as being like the brakes of a car and the brakes aren’t working for people with Alzheimer’s,” LaFerla said in the press release. “This research shows that fixing the brakes at the molecular level could provide an entirely new therapeutic avenue. With millions of people affected by Alzheimer’s and the numbers growing, we must research a diverse portfolio of approaches so we can one day vanquish this terrible disease.”
I appreciate the information provided on this site via interviews and articles.
New research links women’s reproductive health and dementia. As a woman facing the possibility of future dementia, I was wondering if there are any support groups your team/organization is aware of for those in this category.
I see my parents’ struggles as my dad cares for my mom who suffers from dementia. The cost of caring for one with dementia is particularly burdensome. Is there any good news in terms of quality, compassionate, and affordable care for those with dementia? I would be interested in information on these topics.
Thank you supporting those who suffer and those who care for them.
I just resigned from my career to care for my husband, who has Alzheimer’s.
I am curious regarding anti inflammatory supplements that might helpful and would like to know what’s being considered. Is turmeric one?
Yes!! Curcumin from turmeric is one, expecially the lipidated form of curcumin fournd in Theracurmin. It was found in a sudy by Dr. Gary Small at UCLA to: remove amyloid plaque, remove tau, and improve memory.
Although I’m not a researcher, I am a LPT and I have personal experience, with family that has extensive Inflammation issues; I’ve been saying for yrs that there has to be some type of connection with the inflammatory of joints regardless of degenerative, or rheumatoid and with Alzheimer’s/dementia. My grandmother, her 5 sisters, and her 2 daughters all had inflammation and all died of Alzheimer’s Brian disease…. There has to be something on our DNA Chain, and perhaps a connection to the 28th Chromosome, that is a connection to be predisposed to this inflammation. Wish we knew more about the Brain, than we do about the Heart. Our Brain, tells us everything if we would just listen, we have known about Alzheimer’s Brain disease since 1906 when the hell are we going to listen to our bodies….??????????
Interesting. I wonder if the increase of the TOM1 protein is manageable through diet or exercise?
After cerebral bleeding in 2004, my wife was diagnosed with dementia in 2009 and gradually lost many facilities. Now 10 years later she cannot eat, nor walk, nor wash, nor dress or undress by herself and needs help for that by myself and for body care, dress and undress by external hospital services (spitex) who come 4 times a day to our home and which I assist. My wife spends 4 + 3 = 7 hours a day in a wheel chair, the balance in bed. She benefits of physiotherapeutical assistance once a week and we do some walking with her then. Plus short distances twice a day. My wife celebrates here 75th birthday, today, and I am 3 years older, we are married since 1966. Caring for her at home with spitex help is the best solution, as this is the environment she is used to since 45 years and I am around, for as long as I am able to care for her, do the cooking and housework, plus garden. Stay in an external home for aged people is much more expensive and would ruin my wife’s health in very short time, as she would not understand anymore where she is, they would ruin her health with heavy chemical drugs. And I fight that we can stay together, this allows her health to remain stable. If you have questions please write.
Dear Ulrich,
Your letter was very inspiring. Your wife is very fortunate to have such a compassionate and caring spouse. That you are willing to go the distance for her is a testament to the many wonderful years you shared together, I’m sure.
Sounds like Medicaid home care. References to Spitex are in German or similar language.
I love that you take the best care you think will benefit your wife and her needs. Cudoos to you. My Daddy died from Alzheimers related illness. It it not easy to care for or pay for the care needed. You are a special spouse. Hope your children and relatives love and appreciate you.
thank you for your information. most interesting .
I’d liked more information on how one gets TOM-1 in a diet? I have no idea where this might come from, and how to prevent consumption in my diet. Or is this something that I can do anything about?
Any proteins that are eaten are normally digested, and therefore no longer active. TOM-1 appears to be produced inside the brain instead.
Also, you want more TOM-1, not less.
More research is needed on whether anything in your diet affects how much TOM-1 is produced.
My husband is currently in home hospice and I’m his primary caregiver. He is unable to speak and is totally dependent on others for his care. He also has an inherited central nervous system disorder, essential, or familial, tremor, from which his father also suffered. Signs of dementia started in 2013, and he was diagnosed with dementia and Parkinsonism in 2015. His sister has a very slight tremor, no dementia but severe arthritis, having had both hips and both knees replaced. Neither Alzheimer’s nor Parkinson’s medications had any effect on my husband’s condition. I suspect that his dementia is related to his inherited disorder, and I’m very interested in any research on the relationship between inflammation and dementia in general. His neurologist has explained that his condition is related to an inflammatory process.
Try checking the source of the inflammation – toxic chemicals in common, everyday products; especially fragrances which have unreasonable privacy protections. People do not realize how toxic their fragrances are until they develop Multiple Chemical Sensitivity and can no longer breath the same air as the people around them who are wearing, spraying or diffusing fragrant products. The damage these everyday items are doing is gradual (unless there is a sudden large exposure) and most people simply think they have untreatable allergies. However, the body is responding to a foreign object. In my case, I accidentally discovered that anti-cholinergics help and the mechanism is to prevent choline from binding to neurotransmitters; a job that cholinesterase should be doing rapidly.
I am MOST interested in reading the responses to the several questions above.
THANK YOU ahead of time for keeping us informed!
Jo Sanders
p.s. I have 2 deceased paternal aunts that died as a result of Alzheimer’s disease.
I was diagnosed with Alzheimer’s over 10 years ago by a nuerologist (whose mother had Alz). The docter did an MRI, a B12 test. and had a specialist do a 90 minute memory & cognative test. As you can tell by this comment I am still functioning, although with increased loss of memory. I would be more than willing to describ how I have managed my struggle against Alzheimer’s.
Thank you for the interesting research regarding TOM1. Please continue to update me as my family struggles with this disease.
How does one increase TOM 1 ?
I am unsure of the difference between Alzheimers and senile dementia.
I am still functioning fairly well to a certain extent but people who have not been warned get annoyed with me because I repeat something I said five minutes ago. I feel like a pariah and my partner of nearly five years is now disgusted with me and has ejected me from his flat. His own son suffers from autism. Fortunately I have my own flat and a kind daughter but she lives elsewhere and plans to go off to live in the Alps with her boyfriend. I dread getting worse. I still love listening to opera. It is my consolation. My mother’s partner became terribly cruel and mocking towards her and she was so sad. I do not wish to give my name here. Please respect my anonymity.
The article does not give any suggestions for how to increase TOM-1 protein. Identifying the problem is good, but unless and until we’re provided with information on how to try to fix the problem, it’s not very helpful.