The NAD+ Breakthrough That Could Prevent — or Even Reverse — Alzheimer’s Disease
A landmark study suggests restoring NAD+ may protect brain energy, reduce Alzheimer’s markers, and support cognitive resilience.
It was November 1901 when a German neurologist named Alois Alzheimer first met a 51-year-old woman called Auguste Deter at the Frankfurt Psychiatric Hospital. She was confused, disoriented, and terrifyingly young to be losing her mind. When Alzheimer asked her what she was doing, she answered: “Ich habe mich verloren.”
“I have lost myself.”
She died on April 8, 1906. Alzheimer performed an autopsy on her brain and found two abnormal structures we now call amyloid plaques and tau tangles, and since that day, those two features have been the defining image of Alzheimer’s disease (AD): the enemy, the target, the thing we had to destroy.1
For 120 years, we have poured billions of dollars into attacking those plaques. And for 120 years, the results have been disappointing. Not because the science was wrong, but because, as a stunning new paper published in Cell Reports Medicine in December 2025 suggests, we may have been looking at the wrong thing entirely.2
55 Million Reasons to Pay Attention
Right now, more than 55 million people worldwide live with dementia, and Alzheimer’s disease accounts for the majority of those cases.3 By 2050, that number is projected to reach 153 million, almost triple today’s figure.4
Every 3 seconds, someone in the world develops dementia.3
If Alzheimer’s hasn’t touched your life yet, it will. A parent, a partner, a friend, or yourself. A 2025 analysis estimated the lifetime risk of dementia after age 55 at 42%, more than double what we previously thought.5
And until very recently, the medical consensus was brutally clear: once Alzheimer’s starts, it cannot be reversed. You could slow it down, perhaps. You could hope to delay it. But reverse it? Recover from it? Impossible.
That was the dogma. Since Alois Alzheimer’s microscope first revealed those plaques in 1906.
Until now.
The Paradox That Nobody Talks About
Here is something your doctor probably never told you, and I think they should have.
Amyloid plaques, the central villain in the Alzheimer’s story, do not reliably cause the disease.
Between 20% and 50% of people who die with large amounts of amyloid in their brains never develop dementia. They stay sharp, functional, and cognitively intact until the end of their lives.6 Researchers call these individuals NDAN: Non-Demented with Alzheimer’s Neuropathology.
Think of it like this: imagine a city where some buildings have cracks in their walls. Some buildings with cracks collapse. Others stand for decades. The cracks alone don’t determine the outcome, something else does. The question is: what is protecting some brains from collapse?
The 2025 study had an answer. And it pointed not to plaques, but to a molecule you may have heard of: NAD+.
What Is NAD+, and Why Should You Care?
NAD+ — nicotinamide adenine dinucleotide — sounds like something reserved for biochemistry textbooks. But stay with me, because understanding this molecule may be one of the most important things you do for your brain health.
Think of NAD+ as the electricity running through your cell’s power grid. Every cell in your body needs it to generate energy, repair DNA, fight inflammation, and keep its mitochondria (the tiny power plants inside your cells) functioning. Without NAD+, the whole system goes dark, not slowly, but fast.
Here is the critical problem: NAD+ levels fall with age. Significantly. By some estimates, we lose around 50% of our NAD+ for every 20 years of life.7 This decline accelerates with poor sleep, chronic stress, excessive alcohol, and poor diet — factors that happen to describe the lifestyle of a large portion of the modern world.
When NAD+ drops, mitochondria fail. DNA damage accumulates. Inflammation rises. Neurons become vulnerable.
Sound familiar? It should, because that is exactly what happens in Alzheimer’s disease.
The Study That Changed Everything
A research team from Case Western Reserve University, University Hospitals, and the Louis Stokes Cleveland VA Medical Center published their findings in Cell Reports Medicine on December 22, 2025.2 The lead author was Kalyani Chaubey, working with senior author Andrew A. Pieper, MD, PhD, director of the Brain Health Medicines Center at the Harrington Discovery Institute.
What they found is extraordinary.
Using multiple animal models of Alzheimer’s disease, each driven by different genetic causes, the team confirmed that brain NAD+ levels drop dramatically as the disease progresses. They then tested whether restoring those levels could make a difference.
It did.
Using a compound called P7C3-A20, which works by restoring the brain’s NAD+ balance rather than simply flooding it with NAD+, the researchers showed:
In mice treated before the disease fully developed: Alzheimer’s pathology was prevented.
In mice treated after advanced Alzheimer’s had already set in: the disease was reversed. Cognitive function was fully restored. Plaques and tangles, blood-brain barrier damage, oxidative stress, DNA damage, and neuroinflammation all normalized.2
“Restoring the brain’s energy balance achieved pathological and functional recovery in both lines of mice with advanced Alzheimer’s,” said Dr. Pieper. “Seeing this effect in two very different animal models, each driven by different genetic causes, strengthens the new idea that recovery from advanced disease might be possible in people with AD when the brain’s NAD+ balance is restored.”8
Notably, the treatment also reduced p-tau217 — a protein now used as a standard blood biomarker for Alzheimer’s in human patients — providing an objective, measurable confirmation that the disease was being reversed.2
This is what makes this paper different from so many Alzheimer’s studies before it. It doesn’t just report one outcome in one model. It shows coherent, cross-validated results in multiple animal lines, with a mechanism that maps onto what we see in human brains.
But Here Is Where It Gets Really Interesting
Remember NDAN, those people with plaques who never got dementia?
The 2025 study found that one of the key biological differences between those resilient brains and the brains of people who did develop Alzheimer’s was, you guessed it: NAD+ levels.2
The people who maintained higher brain NAD+ were somehow buffered. The metabolic machinery of their neurons kept running despite the presence of amyloid, the same way some buildings stay standing despite having cracks in the walls.
It raises a question that every reader of this newsletter should be sitting with right now:
What are you doing, today, to protect your brain’s NAD+ levels?
🔒 The rest of this post is for paid subscribers.
Inside, I break down the complete evidence-backed NAD+ protocol — including what the human clinical trials on NMN and NR actually show, what natural lifestyle habits have been proven to protect and restore NAD+, what depletes it faster than aging, and the step-by-step checklist you can start this week.