Is Alzheimer’s an Infection? How the Brain’s Immune System Might Hold the Answer

When we think about the immune system, most of us picture white blood cells fighting off a cold or healing a cut. But here’s something crucial to keep in mind: your brain has its own immune system that works entirely different than the rest of your body.

As our foundation funds research into the microbial / infectious hypothesis of Alzheimer’s, this idea of our brain having its own immune system is very important. Especially in instances where something foreign ( a bacterial, viral or fungal cell ) gets past the blood brain barrier. 

Let’s break it down.

Glial cells are the unsung heroes of the brain’s immune and support systems. The word “glia” means “glue” in Greek—but they do way more than just hold things together.

There are several types of glia, but for brain cleaning and immune function, the most important are:

• Astrocytes: Star-shaped cells that help with repair, maintain the blood-brain barrier, and regulate nutrients and neurotransmitters. They’re key players in waste clearance.
• Microglia: The immune cells of the brain. They detect threats like infections or debris and send out cytokine alerts to coordinate a response.

Microglia are essentially the Brain’s Bodyguards

Meet the microglia — these tiny (thus the term micro), spider-shaped cells are basically the brain’s built-in security guards. They’re constantly patrolling, looking for anything that shouldn’t be there (like viruses, bacteria, or dead cells). If they find trouble, they sound the alarm and start cleaning things up.

But microglia aren’t just there for emergencies. They also help keep your brain working smoothly by pruning weak or unused connections between brain cells. Kind of like a gardener trimming branches to help the tree grow better.

Astrocytes: The Helpers That Do Everything

Next up: astrocytes. These star-shaped cells are the multitaskers of your brain.

• They bring nutrients to your brain cells.
• They help control what gets in and out of your brain’s blood supply.
• They even clean up chemical messes after brain cells “talk” to each other. We often refer to this as the “metabolic debris” that accumulates all day long as you walk, talk, think, eat and read your best friend’s Facebook post about her new puppy.

Astrocytes are like backstage crew at a concert—if they weren’t there, the show wouldn’t run.

Learning & Healing: BDNF and Cytokines

Let’s talk molecules.

BDNF (brain-derived neurotrophic factor) is a mouthful, but think of it as Miracle-Gro for your brain. It helps your brain grow, heal, and learn. You make more BDNF when you exercise, sleep well, or challenge yourself to learn something new.

On the flip side, cytokines are like text messages your immune system uses to send alerts. Some are anti-inflammatory—they help calm things down and keep your brain balanced. Others are pro-inflammatory—they jump into action when there’s a threat, like an infection. But when your body sends too many of the wrong messages (especially during stress, poor sleep, or chronic infections), it creates ongoing inflammation in the brain. That kind of constant “brain fire” can damage brain cells and make it harder to think clearly or remember.

So, who sends out these cytokine alerts?

Think of your brain like a high-tech city. When there’s trouble—like a virus sneaking in, a head injury, or a long-term bacterial infection (like from gum disease)—your brain’s security guards (remember the microglia from earlier?) sound the alarm. Microglia are like firefighters and paramedics rolled into one. They scan the scene, then call for cytokines to come check it out.

Some cytokines are just informational…

“Hey, there’s a mess to clean up.”

Others hit the panic button and scream…

“This is serious!”

…in effort to bring in heavy reinforcements. If it’s a quick fix—like clearing out a dying cell—the cytokine response wraps up fast. But if the problem is ongoing and unresolved, like with chronic bacterial infection, the alerts don’t stop. The emergency system keeps firing, and eventually, it goes haywire. Instead of helping, it starts harming healthy brain cells—causing swelling (inflammation), confusion, and over time, even memory loss.

And then there’s the Night Crew: The Glymphatic Team who clean while you sleep

Ever wonder why sleep is so important? Well, while you’re deep asleep, your brain uses a vacuum of sorts called the glymphatic system to collect and flush out waste, including that metabolic debris mentioned earlier as well as any other “junk” left behind by immune battles that took place during your day.  Think lymphatic but using

Yep. Your brain literally cleans itself at night. That’s why pulling all-nighters can leave you feeling foggy and slow.

When the Brain’s Immune System Goes Wrong

But just like any system, things can break down. If microglia or astrocytes go into overdrive—or if your body sends too many inflammatory cytokines to the brain—it can cause problems. Scientists think this may play a role in conditions like Alzheimer’s Disease.

As a quick review: 

• Your brain has its own immune system, separate from the rest of your body.
• Glial cells = the brain’s behind-the-scenes support team (includes microglia & astrocytes).
• Microglia = bodyguards & clean-up crew (they fight infections and eat up debris).
• Astrocytes = support squad & chemical managers (they guide nutrients and help with brain detox).
• BDNF = brain fertilizer; helps neurons grow and form new connections.
• Cytokines = immune text messages; helpful alerts in small amounts, harmful when constant.
• Glymphatics = the brain’s night shift janitors; they flush out toxins, mostly during deep sleep.

So, if you want your brain to stay sharp: sleep, move, learn, and chill out. Your brain’s immune squad will thank you.

This overview of the brain’s immune system is helpful when understanding the reason the CAD Foundation is funding research into how long-term infections—like those caused by gum disease—might quietly spark this immune overreaction that leads to Alzheimer’s. 

1. Mechanistic insights into the role of amyloid-β in innate immunity 2024 Journal of Nature Tatum Prosswimmer, Anthony Heng & Valerie Daggett   https://www.nature.com/articles/s41598-024-55423-9

ABSTRACT: Colocalization of microbial pathogens and the β-amyloid peptide (Aβ) in the brain of Alzheimer’s disease (AD) patients suggests that microbial infection may play a role in sporadic AD. Aβ exhibits antimicrobial activity against numerous pathogens, supporting a potential role for Aβ in the innate immune response. 

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2. In 2024, the amyloid-cascade-hypothesis still remains a working hypothesis, no less but certainly no more 2024 Frontier Christian Behl^* https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1459224/full

CONCLUSION: Interestingly, the amyloid-cascade-hypothesis is a prime example for an idea presented by the philosopher Thomas S. Kuhn on trajectories of scientific paradigms (Kuhn, 1970). Kuhn’s discerns three key phases in science and in the evolution of scientific progress: (1) the preparadigmatic phase of science (competing views and approaches exist), (2) the paradigmatic phase of science (one particular paradigm dominates field), and (3) the revolutionary phase (certain inconsistencies and anomalies trouble the current theory, which is attacked and under pressure; novel views appear). This ultimately culminates in a paradigm shift and a scientific revolution. Regarding the amyloid-cascade-hypothesis, I would say, we are not quite there yet; we have not reached the final steps of stage 3, the necessary paradigm shift. Very likely, it will take more time to get there, and the amyloid-cascade will continue to be the basis of many basic, preclinical, and clinical research which is already ongoing or planned. Yet, in my personal view and as written in the headline of this discussion, in 2024, the amyloid-cascade-hypothesis still remains a working hypothesis—no less but certainly no more.