I’ve been reading a lot of Alzheimer’s research lately and it’s frustratingly myopic.
Most of it follows the same pattern: “Here’s a drug that might slow things down by 6 months” or “This compound reduced plaques by 15% in mice.” Unfortunately, our modern view of scientific research focuses on single compounds and single-targets. But leading thinkers are at the same time coming to the conclusion that humans are incredibly complex systems, so researching a single target intervention is always to come up short.
Then I came across this comprehensive review by Chen et al., published in Biomedicine & Pharmacotherapy in 2024 about reishi mushroom and the brain.
These researchers systematically reviewed everything we know about Ganoderma lucidum (better known as Reishi or Lingzhi) and its effects on Alzheimer’s disease. What they found is a perfect illustration of how nature approaches complex problems differently than the pharmaceutical industry does.
Multi-Target
While modern medicine tries to find the single mechanism behind Alzheimer’s – is it the amyloid plaques? The tau tangles? The inflammation? – Reishi treats the whole and addresses all of them simultaneously.
The review documented that Reishi and its bioactive compounds work through at least eight distinct mechanisms:
- Inhibiting tau hyperphosphorylation (those tangles that strangle neurons)
- Blocking amyloid-β formation and promoting its clearance
- Calming overactivated microglia (your brain’s immune cells gone rogue)
- Regulating the NF-κB/MAPK inflammatory pathways
- Preventing neuronal death
- Modulating immune function
- Inhibiting acetylcholinesterase (preserving the neurotransmitter crucial for memory)
- Supporting mitochondrial function and reducing oxidative stress
This is systems-level intelligence.
Brain Energy
Let’s talk about what’s actually happening in an Alzheimer’s brain, because this is where Reishi’s multi-pronged approach makes perfect sense.
Alzheimer’s isn’t just a plaque problem. It’s fundamentally an energy crisis. Your neurons are the most energy-demanding cells in your body, consuming about 20% of your total energy despite making up only 2% of your body weight. They’re powered by mitochondria, those cellular power plants we’re finally starting to appreciate.
In Alzheimer’s, mitochondria start failing. The research Chen and colleagues reviewed showed that compounds in Reishi (particularly ganoderic acids and polysaccharides) directly support mitochondrial function. Ganoderic acid D, for instance, improved mitochondrial complex I activity, reduced reactive oxygen species, and enhanced energy production through oxidative phosphorylation.
When your brain cells can’t generate sufficient ATP (cellular energy currency), everything else cascades. They can’t clear out damaged proteins, they can’t maintain their membranes, and they can’t communicate properly. They become vulnerable. This is where inflammation starts – as a response to metabolic distress.
Inflammation is a Signal
We talk about neuroinflammation like it’s purely destructive, but that’s not quite right. Inflammation is your brain trying to clean up and repair. The problem in Alzheimer’s is that this cleanup crew (primarily microglia) gets stuck in overdrive and starts causing collateral damage.
Here’s where Reishi does something fascinating. Rather than simply “reducing inflammation” (the sledgehammer approach), compounds like ganoderic acid A actually shift microglia from their destructive M1 state to their healing M2 state. So they’re not suppressing your immune system. It’s more accurate to say that they’re redirecting it.
The researchers found that Reishi components inhibited pro-inflammatory signaling through the NF-κB pathway while simultaneously promoting anti-inflammatory factors and even BDNF (brain-derived neurotrophic factor). BDNF is a crucial protein that helps neurons survive, grow, and form new connections.
This is a perfect example of how certain mushrooms promote long term health. They don’t suppress symptoms. They actively promote repair while improving your internal environment for long term health to flourish. They represent a completely different paradigm to our current healthcare system.
Neuroplasticity
One of the most exciting findings buried in this review is that Reishi polysaccharides promoted neural progenitor cell proliferation in both healthy and neurodegenerating brains. Even in APP/PS1 mice (a standard Alzheimer’s model), treatment increased neurogenesis (the growth of new brain cells).
We’ve been told for decades that you can’t grow new brain cells. Then we learned you can, but it drops off dramatically with age and disease. But here’s a mushroom extract actively stimulating the birth of new neurons in diseased brains.
This connects to something deeper about how we think about cognitive decline. The conventional view treats it as inexorable deterioration. A gradual loss of what you had. But what if significant aspects of cognitive aging are actually metabolic and inflammatory suppression of your brain’s inherent regenerative capacity?
Think about it like this. If your gut replaces its entire lining every few days and your skin regenerates constantly, why would your brain lack sophisticated renewal mechanisms? It doesn’t. We’ve just been suppressing them with poor metabolic health, chronic inflammation, and oxidative stress. Mic drop.
Decentralised Brain Health
There’s something philosophically important here about how we approach medicine.
The dominant paradigm seeks silver bullets. One drug, one target, one disease. It’s centralised thinking. Find the master switch and flip it.
But complex systems – whether they’re ecosystems, economies, or brains – don’t have master switches. They have networks, feedback loops, and redundancies. When you try to control them from a single point, you get unintended consequences.
Reishi’s approach is fundamentally decentralised. Its hundreds of bioactive compounds work across multiple pathways simultaneously. Ganoderic acids target inflammation and tau phosphorylation. Polysaccharides modulate immunity and support neurogenesis. Triterpenes scavenge free radicals and support mitochondria. Together, they create a coordinated effect that no single compound could achieve.
This is how nature works. And increasingly, it’s how we’re learning complex diseases work.
First Principles: What Does a Brain Actually Need?
Strip away all the molecular biology for a moment. What does a neuron fundamentally need to function?
- Energy (mitochondrial ATP production)
- Structural integrity (protected membranes, stable proteins)
- Clean environment (removal of damaged components)
- Communication capacity (neurotransmitters, receptors, synaptic connections)
- Regenerative support (growth factors, building blocks for repair)
Reishi addresses every single one of these fundamental needs. Evolving over millions of years, these mushrooms have been responding to environmental stressors, developing compounds that help them survive oxidative stress, compete with pathogens, and adapt to changing conditions.
Many of those same stressors affect our cells. The solutions mushrooms evolved (antioxidants, immune modulators, and metabolic regulators) turn out to work in our biology too.
The Takeaway
If you’re reading this because you’re concerned about your own cognitive health or that of someone you love, here’s what I take from this research:
Alzheimer’s isn’t just genetic destiny. The disease involves multiple metabolic failures – energy production, waste clearance, inflammatory regulation, and oxidative stress management. These are all influenced by lifestyle, and they can potentially be supported.
Cognitive decline follows metabolic dysfunction. Your brain is an energy hog. When mitochondrial function falters, when inflammation becomes chronic, and when oxidative stress overwhelms your defenses, that’s when things start breaking down. Reishi targets these fundamental processes.
Earlier is better than later. By the time clinical Alzheimer’s is diagnosed, decades of pathology have accumulated. The compounds in Reishi that promote neurogenesis, support mitochondrial function, and modulate inflammation make sense as preventive tools, not just treatments.
No single intervention is sufficient. Reishi works through multiple mechanisms, but it’s still one piece. Sleep, metabolic health, exercise, stress management, community connection – these aren’t optional extras. They’re the foundation.
The Bigger Picture
Reading through this 20,000+ word review, I kept coming back to one thought. We’ve been thinking about brain disease backwards.
We’ve treated Alzheimer’s as a discrete entity, as a specific disease to attack with specific drugs. But maybe it’s better understood as what happens when multiple protective and regenerative systems fail simultaneously. The plaques and tangles aren’t the disease. They’re simply the debris of metabolic collapse.
And if that’s true, then supporting those fundamental systems (energy production, inflammatory balance, oxidative defense, regenerative capacity) shouldn’t be dismissed as “alternative” medicine. It should be considered first-principles medicine.
Reishi won’t cure Alzheimer’s. But it might help restore some of the conditions under which your brain can defend and repair itself. And given its safety profile and its multiple mechanisms of action, it represents exactly the kind of tool we should be investigating more seriously.
Buy Reishi extracts here.
The full study: Chen XJ, Deng Z, Zhang LL, et al. “Therapeutic potential of the medicinal mushroom Ganoderma lucidum against Alzheimer’s disease.” Biomedicine & Pharmacotherapy. 2024. https://doi.org/10.1016/j.biopha.2024.116222
