Alzheimer’s Mystery Solved: “Angry” Immune Cells in Brain and Spinal Fluid Identified As Culprit

Headache Pain Brain Neck Spinal Cord Illustration

Scientists have discovered the role of cerebrospinal fluid in cognitive impairment, such as Alzheimer’s disease.

Immune cells in brain and spinal fluid become dysregulated and ‘a little angry’ as we age.

  • Cerebrospinal fluid immune system is drastically altered in individuals with cognitive impairment
  • Discovery could potentially be used to treat inflammation of the brain 
  • First thorough analysis of important brain immune system 

The reason your three-pound brain doesn’t feel heavy is because it floats in a reservoir of cerebrospinal fluid (CSF), which flows in and around your brain and spinal cord. This liquid barrier between your brain and skull protects it from a hit to your head and bathes your brain in nutrients.

But the CSF has another critical, if less known, function: it also provides immune protection to the brain. Yet, this function hasn’t been well studied.

A Northwestern Medicine study of CSF published on December 13 in the journal Cell, has discovered its role in cognitive impairment, such as Alzheimer’s disease. This discovery provides a new clue to the process of neurodegeneration, said study lead author David Gate, PhD, assistant professor in the Ken and Ruth Davee Department of Neurology.

The study found that as people age, their CSF immune system becomes dysregulated. In people with cognitive impairment, such as those with Alzheimer’s disease, the CSF immune system is drastically different from healthy individuals, the study also discovered.

“We now have a glimpse into the brain’s immune system with healthy aging and neurodegeneration,” Gate said. “This immune reservoir could potentially be used to treat inflammation of the brain or be used as a diagnostic to determine the level of brain inflammation in individuals with dementia.”

“We provide a thorough analysis of this important immunologic reservoir of the healthy and diseased brain,” Gate said. His team is sharing the data publicly, and its results can be searched online.

To analyze the CSF, Gate’s team at Northwestern used a sophisticated technique called single-cell RNA sequencing. They profiled 59 CSF immune systems from a spectrum of ages by taking CSF from participants’ spines and isolating their immune cells.

The first part of the study looked at CSF in 45 healthy individuals aged 54 to 83 years. The second part of the study compared those findings in the healthy group to CSF in 14 adults with cognitive impairment, as determined by their poor scores on memory tests.

Gate’s team of scientists observed genetic changes in the CSF immune cells in older healthy individuals that made the cells appear more activated and inflamed with advanced age.

“The immune cells appear to be a little angry in older individuals,” Gate said. “We think this anger might make these cells less functional, resulting in dysregulation of the brain’s immune system.”

In the cognitively impaired group, inflamed T-cells cloned themselves and flowed into the CSF and brain as if they were following a radio signal, Gate said. Scientists found the cells had an overabundance of a cell receptor — CXCR6 — that acts as an antenna. This receptor receives a signal — CXCL16 — from the degenerating brain’s microglia cells to enter the brain.

“It could be the degenerating brain activates these cells and causes them to clone themselves and flow to the brain,” Gate said. “They do not belong there, and we are trying to understand whether they contribute to damage in the brain.”

Gate said his “future goal is to block that radio signal, or to inhibit the antenna from receiving that signal from the brain. We want to know what happens when these immune cells are blocked from entering brains with neurodegeneration.”

Gate’s laboratory will continue to explore the role of these immune cells in brain diseases like Alzheimer’s. They also plan to expand to other diseases, such as amyotrophic lateral sclerosis (ALS).

Reference: “Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment” by Natalie Piehl, Lynn van Olst, Abhirami Ramakrishnan, Victoria Teregulova, Brooke Simonton, Ziyang Zhang, Emma Tapp, Divya Channappa, Hamilton Oh, Patricia M. Losada, Jarod Rutledge, Alexandra N. Trelle, Elizabeth C. Mormino, Fanny Elahi, Douglas R. Galasko, Victor W. Henderson, Anthony D. Wagner, Tony Wyss-Coray and David Gate, 13 December 2022, Cell.
DOI: 10.1016/j.cell.2022.11.019

Other Northwestern authors are Natalie Piehl; Lynn van Olst, PhD; Abhirami Ramakrishnan; Victoria Teregulova; Brooke Simonton; and Ziyang Zhang.

This work was in part supported by a National Institute on Aging (NIA) grant A R01AG078713-01, a 10x Genomics Early Career Investigator Award, a National Institute of Neurologic Disease and Stroke K99/R00 Pathway to Independence Award NS112458-01A1, NIA R01AG045034 05, the NIA funded Stanford ADRC P50AG047366, and P30AG066515, R01AG048076, all of the National Institutes of Health.

Other support was from UC San Diego Shiley-Marcos grant, a pilot project through the Northwestern University ADRC, an Irene Diamond Fund/AFAR Postdoctoral Transition Award in Aging, the Cure Alzheimer’s Fund, the Alzheimer’s Association NIA R01AG04503405, the NIA funded Stanford ADRC P50AG047366 and P30AG066515, R01AG048076.

47 Comments on "Alzheimer’s Mystery Solved: “Angry” Immune Cells in Brain and Spinal Fluid Identified As Culprit"

  1. So my Alzheimer’s is because my head-juice is angry at the radio?

    Quit your scientific techno jive talking and give it to me straight doc.

  2. The T cells are there.. More than likely do to infection…

  3. Dimentia / Alzheimers and Multiple sclerosis exists in my family. I’m not surprised with these results. Unfortunately just a generation ago, there wasn’t much info. On these diseases. Let’s hope 🙏 they are making some progress.

  4. Good article.

  5. As a Massage Therapist I am wondering if gentle lymphatic drainage scalp massage could help the flow of the brain fluids. There are so few Crainial Sacral therapist but much scalp massage technics come from India and Asia.

  6. A published scientific paper isn’t an announcement. Research is published so that other scientists can either replicate or experimentally refute the results. No science should be published without explaining this.

  7. I have advanced degenerative disc disease and have mild cognitive impairment.

  8. I forgot to add this in my last post. I have also have developed an immune problem. 2000watt I have enlarged lymphnodes in lungs that won’t go away, and have had shingles on the right side of face. I’m just curious if there is a connection regarding the research.

  9. Will now sign up as test subject 88 healthy male

  10. Cure the disease and kill the golden goose.

  11. Charles G. Shaver | December 27, 2022 at 8:28 am | Reply

    Again, they fail to factor-in long-term chronic subclinical non-IgE-mediated food allergies and FDA approved food poisoning. “Angry cells?” Not as angry as I am that the keep ignoring me, after writing more than 3,000 more authoritative, qualified and/or resourceful professional others of my rare (if not unique) lay findings over the past seventeen years, beginning with the FDA (with replies) about allergies, added MSG, chronic disease and obesity in October of 2005.

  12. What an idiotic opening sentence. The writer obviously failed physics. With that lack of credibility, I have not read any further.

  13. Mario Antwan Montgomery | December 27, 2022 at 11:03 am | Reply

    I was told by spirit that memory is actually stored in the spine. I think the brain is a spirit interpreter. Is it a coincidence that the spinal fluid has to do with a memory loss disease? I don’t think so. I got to give credit to the spirit that told me. I just don’t know it’s name. I was trying to figure out how to fix spinal injuries with the spirit of Casey at the time.

  14. Does Alzheimer has anything to do with Cerebellar ataxia as it causes movement/balancing issues.

  15. This is something I have believed from long ago I now have been proven correct.. meaning to whoever can do something with this next part of information will make history…to cure or clean CSF fluid one must figure out how to flash highly concentrated light into the spinal and brain to purify to contaminate CSF FLUID just as the sunlight helps clean the air so the light will change the CSF FLUID

  16. When can I get the anti-jerk (no social grace) vaccination. I always say the wrong things at the worst time. I’ve heard of Behavior Correction Spray but Santa didn’t deliver. His elf told me that high-priority gift was given to world leaders (Putin and others) and hard to come by. Help!

  17. The headline over-sells the article. What was discovered is not a solution to Alzheimer’s. It is more like a clue. (Hint: notice how often the lead author of the scientific paper is quoted as using words like “might” and “potentially could”. )

  18. Mary Ann Hadley | December 27, 2022 at 5:59 pm | Reply

    As a Registered Nurse, I find this type of language condescending and even repulsive. Does the author really believe that people think immune cells can be “angry”? Or that brain cells can send out “radio waves”? 21st century readers have access to Wikipedia. If there’s a word they don’t understand, they look it up. This type of writing does not reveal useful information. Does this website even have an editor? As a nurse who likes to read about scientific advancement, I think I can eke out some bits of information from this writing, but I come away feeling insulted. Send it back for a rewrite.

  19. Yes, and if your pregnant you can only take Tylenol. These studies are funded by people that won’t take results that expose them to liability.

  20. I have idiopathic intracranial hypertension, where there is an increase of fluid around my brain. Memory has always been off. Wonder if there is any connection.

  21. I was just reading an study on Alzheimer’s where this scientist found these parasites in every person with an Alzheimer diagnosis. He performed a spinal tap and all of the subjects had these parasites in their spinal fluid. He speculates that as parasites often cause havoc in our bodies maybe they are the cause of all of these immune illnesses and in this country very few doctors have the foresight to even contemplate that one might be infested with parasites that no one bothers to test for them. He published his findings a year ago. But of course there’s no profits in curing people from parasites so there’s no cure for so many autoimmune illnesses.

  22. The title of this article is exactly the problem with journalism today. Some person discovers an article, someone else edits it and some half-wit titles it.

    It’s off the mark, makes outlandish claims and disregards the data.
    It’s people like you [writers] that have left the masses of people hung out to dry, believing whatever clickbait jargon you spit out.
    Fast forward 10 years, anti vaxxers and holistics are clogging our society like beta-amyloid plaques.

    Go home. You’ve done enough damage today. Let’s let the adults take it from here.

  23. Lane Scott, PhD | December 28, 2022 at 7:33 am | Reply

    Interesting article. Need more information and research.

  24. Well, it’s a clue. The main villain/villains may yet to be discovered. But I hope these investigators don’t stop here. I hope this important step provides encouragement and funding for more research on this heartbreaking disease.

  25. NAC helps reduce CXCR6. Also many studies show benefits for those with Alzheimers.

  26. Gee… wonder if it has anything to do with all of the flu and various vaccines they talk people into causing this dysregulation. Maybe even a cumulative affect.
    Nah. Can’t possibly be that.

    • Nope can’t possibly since this has been around since the beginning of human-kind and vaccines are less than a hundred years old. Iyiyi.

  27. Very impressive! Great work. I love the detail description and determination to understand. Keep up the good work

  28. My Dad has Alzheimer’s Dementia and is in a specialized care facility. Every single day I wonder why there is no research being done with these people? I’m not talking about being scanned or poked and prodded, but blood samples periodically or even talking to the family and people like my Dad. There is a lot to be learned from all of us and it is astounding to me that no one is doing this. I see things from him all the time and I know others feel the same. This brutal disease takes everything they were and corrupts it, so maybe some good can come from those that witness it for years and years. Make their end have some meaning

    • Charles G. Shaver | December 29, 2022 at 8:13 am | Reply

      M Clark, my mother (lab tested and known to me to have some food allergies) died of complications of dementia in 1998, my older brother (never tested that I know of) in 2018. I’ve known of my own multiple food and food additive allergies since late 1981, and experienced allergy/added MSG/medical error related calcium and phosphorus deficiency related temporary short-term memory problems in 2009-2010 and 2021-2022, respectively, still addressing the more serious phosphorus deficiency. The most obvious common symptoms of my (Dr. Arthur F. Coca’s; by 1935) kind of long-term chronic subclinical non-IgE-mediated food allergies are obesity, so-called “male pattern baldness” and eyeglasses for myopia. If any of that applies to your father it may not be too late to help him, some, beginning with ionic testing for calcium, bone density testing and uric acid testing. In the absence of adequate dietary supplies of calcium, my kind of allergies can insidiously and subtly cause the body to deny and/or rob the bones, nerves and/or teeth of calcium (minimally), trying to maintain the blood at an optimal pH by neutralizing the uric (minimally) acid. Don’t expect his doctors or nurses to know these things, or that standard blood serum testing is unreliable for calcium (at least). Any prior joint replacements could be additional indications of those. Best wishes to you and your father. I’ll check back for any reply.

      • Hello Charles. I noticed that you mentioned in this and other comments that you did some of your own research. I was wondering if you could share it. I am interested in correlation of Uric Acid levels and and dementia progression.

        • Charles G. Shaver | December 29, 2022 at 12:59 pm | Reply

          Thanks, Rimantas, for asking. Basically I’m a lay ‘single-subject-study’ for 42 years and counting, ineligible for any research grants I ever investigated. My own chronic illness has mostly precluded any lengthy single publication (e.g., a full-length book; several begun and none completed) on my part. I have uploaded a one-page overview and summary of my entire adult illness experience to the “About” page of my non-economic Odysee dot com/@charlesgshaver video channel. Perhaps this extract from that ‘summary’ will meet your immediate needs, sans the possible complications I mention therewith:

          Approximate etiology and pathology of most chronic disease (T = time): subclinical psycho-somatic non-IgE-mediated allergy reactions + offending foods + T + MSG/soy (minimally; less T) > inflammation + T > xanthine oxidase + T > serum uric acid (gout) + ROS (free radicals) + T > immunodeficiency + T > calcium (minimally) loss + T > acidic blood + T > mitochondria switching from glycolysis (glucose-to-energy) to glycogenesis (glucose-to-fat) + T > uric acid deactivating nitric oxide + T > oxidative stress + T > insulin resistance + T > metabolic syndrome (chronic fatigue, aches, pains, muscle weakness and brain fog) + T > chronic/degenerative disease (aging, Alzheimer’s, ALS, AMD, anxiety, bad moods [confusion; depression; mass shootings; suicides], cancer, cataracts, CFS/ME & FM, diabetes, gout, HBP, insomnia, obesity, PD, stroke, tinnitus, tooth loss, etc.) and/or medical error + T > premature disability and/or death.

          I rely on medical lab testing for various blood levels of specified factors. I’ll check back for any additional reply.

  29. Robert Schaffer | December 28, 2022 at 5:36 pm | Reply

    Is it possible that Lyme disease accelerates this. Could it be possible the same treatment may work for Lyme? I would be willing to be a test subject.

  30. Whole lot of “we think” and “possibly” in there to call anything solved.”and we are trying to understand whether they contribute to damage in the brain.”. progress, maybe but not solved

  31. William Bradley | December 29, 2022 at 8:51 am | Reply

    South Sea Islanders will not live on islands with a lot of background aluminum. Their symptoms of alumina poisoning mimic alzeheimer’s.

  32. OH MY GOD! What a ridiculous, absurd article!!!
    Is there ANYONE who understands the difference between “is associated with” and “causes”? The headline is ridiculous. There is LOTS of reason to believe that the Tau and Amyloid changes in the brain with Alzheimer’s would trigger an immune response…NOT that the immune response caused the damage!!!

    And the other crap in this and the source article makes me want to scream!!! “Angry” immune cells? WTF? Are you people that stupid that you cannot use the right terms, or do you think the immune cells have little personalities and emotions?

    And then there are the other fools spouting crap like “It’s the aluminum”…MORE correlation, not causation!

  33. Has craniosacral therapy been used to regulate the CSF..? If not, get with the UPLEDGER Foundation and test it out. You’re welcome. 😁

  34. Sabina D'Onofrio | December 30, 2022 at 1:28 am | Reply

    So,it’s news that spinal fluid supports brain fluid?
    Gee, I thought they were one and the same as my life. Llol
    Viruses harbor within the spinal column. That’s why they thrive in the tonsils.
    So why is it news now??? Why they wanted to confuse us about masks. Dude, one does NOT have to be sick to cough those ACTIVE germs out. Probably a new expensive drug therapy they want us to “need”

  35. Friends I like to share my experiences with my leaky gut autoimmune problems.
    Due to leaky gut I have autoimmune problems, resulting in psoriasis on elbows and also insulin intolerance.
    No inflammation or arthritis.
    I cannot eat high carbs,sugar,milk and milk products.I keep away from beef as it is high on saturated fats.No seed oils only extra virgin olive oil,AVACADO oil.
    Lot of greens 🥬 and chicken,fish or even lamb 🐑 is good.
    I am completely vaccines free for 25 years.I do take immune Surpressants tablets.In June I took two for a week and weaken my immunity as a result I got the flu.Just a mild headache and slight body aches for three day.I got sick after 25 years in Canada.Unfortunately after three days could not eat for 20 days,Lost 30 lbs weight only lived on chicken soup.I could eat on the 21 day after much prayers.THERE IS WHERE THE MIRACLE TOOK PLACE.MY BODY UNDERWENT A COMPLETE REVERSAL AND ALL PSORIASIS AND OTHER ISSUES JUST DISAPPEARED.FASTING IS THE SOLUTION TO AUTOIMMUNE.TRY IT AND YOU MAY BE SHOCKED.

  36. Angelita Castillo | December 31, 2022 at 1:14 am | Reply

    Buen dia
    Me gustaria comprar la version de revista Cell. Donde la venden o suscriben?

    Nuncq oi hanlar de dicha revista dondecaparece esa importante info.

    Gracias y bendiciones

    Nunca la he visto u oido h

  37. Repeat after me: Correlation is not causation. Correlation is not causation. Correlation is not causation.

    This is a correlation at this point, they have no idea about cause.

  38. I’ve been trying to tell people for decades…aluminum plus all the other crap in the poison darts which aren’t allowed to be discussed.. wake up!

  39. I think autoimmune disease has something to do with it!

  40. Northwestern, I wonder if they fully explained to the donors what it was that they were doing. I was there and they took a syringe to my spine; they asked for permission, but to this day, I don’t know for what, I’ve been wondering ever since if it was to inject a slow but deadly disease into my spine. Maybe they do that as well.

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