© Freepik
November 24, 2025
Nils Behrens
Top health expert Nils Behrens on a dangerous alliance: Researchers have discovered that amyloid and fibrinogen together damage the brain much more severely than alone – even in the smallest amounts.
Find a DoctorSearch the network for suitable specialists and contact them directly
Sometimes it is not what is missing, but what is wrongly connected. A new study by Rockefeller University shows that two proteins – amyloid-beta and fibrinogen – together have a devastating effect on the brain. In tiny amounts, which would be harmless on their own, they jointly lead to massive neuronal damage – and significantly accelerate Alzheimer’s processes.
This insight not only adds a new piece to the complex puzzle of the disease, but also new hope for therapies that intervene early – long before memory loss and cognitive failures become visible.
Amyloid-beta (Aβ) and tau proteins have been considered the central ‘suspects’ in Alzheimer’s research for decades. But the simple formula ‘too much amyloid – equals Alzheimer’s’ falls short. Researchers around Prof. Sidney Strickland and Dr. Erin Norris now show that amyloid-beta 42, the particularly toxic variant of the peptide, forms a dangerous alliance with another protein: fibrinogen.
Fibrinogen is actually a harmless component of blood. It ensures blood clotting by being converted into fibrin in case of injuries – a kind of body’s own plaster. However, it should not be present in the brain. Only when the blood-brain barrier, that delicate protective barrier between the circulatory system and nerve cells, becomes permeable – as often happens in the course of Alzheimer’s – does fibrinogen enter brain tissue. There it meets amyloid-beta. And this encounter has fatal consequences.
To investigate the effect, the researchers relied on a sophisticated model: They used tiny slices from the hippocampus of mice – the area where memories are formed. These ‘organotypic brain slices’ stayed alive and responded to the addition of various protein mixtures.
The result was astonishing: Neither amyloid-beta nor fibrinogen alone caused visible damage at low concentrations. However, as soon as both molecules acted together as a complex, synaptic markers—the metric for healthy neuronal communication—collapsed massively. Even tiny amounts of the duo led to the same damage as high doses of amyloid alone.
Nils Behrens, Chief Brand Officer of Sunday Natural and host of the podcast HEALTHWISE
"It takes much larger amounts of amyloid or fibrinogen alone to cause serious neuronal damage," explains study author Erin Norris. "But when both come together, even the smallest doses are enough to trigger significant harm. It's a kind of toxic synergy."
Even more intriguing: When the researchers blocked the binding site through which amyloid docks onto fibrinogen, the effect disappeared. The damage was therefore directly attributable to the complex itself—not merely the presence of both substances.
In further experiments, scientists injected the protein complexes directly into the brains of living mice. Again, the same pattern emerged: Mice that received the preformed amyloid-fibrinogen complexes showed significantly less synaptic activity in the hippocampus—the center of learning and memory.
And it didn't stop at the synapses. The second key player in Alzheimer's, the tau protein, was also found in its pathological, phosphorylated form—an unmistakable signal for the onset of neurodegenerative processes.
Simultaneously, signs of an inflammatory overreaction of the microglia were evident—those immune cells that are actually supposed to protect the brain. Markers such as CD68 and GFAP significantly increased as soon as the complexes were present. Additionally, the blood-brain barrier became more permeable, allowing more fibrinogen and other blood proteins into the brain—a vicious cycle that further exacerbated the damage.
The researchers found increased amounts of fibrinogen and albumin in the hippocampus of the affected animals – both proteins that should not normally be present in the brain. Their presence is a clear sign of a disrupted blood-brain barrier.
"We were able to show that the amyloid-fibrinogen complex itself makes the barrier permeable," says Elisa Nicoloso Simões-Pires, co-author of the study. "That means: What begins as a reaction becomes an amplifier of the disease. More permeability leads to more fibrinogen in the brain, which in turn creates more complexes – a cycle that drives itself."
For a long time, Alzheimer's was considered a purely neuronal disease. Only in recent years has a new picture emerged: the vascular system – microcirculation and the integrity of the blood-brain barrier – also plays a central role.
"Only through recent research have many started to take the vascular contribution to Alzheimer's pathogenesis really seriously," says Norris. "Since our first results, we have been dealing precisely with this mechanism: How does impaired vascular function affect the course of the disease?"
Even in mice where the known microglia receptor Mac-1 was switched off – a previous major pathway for fibrinogen-induced inflammation – the damage persisted. This shows: The toxic effect of the amyloid-fibrinogen complexes follows a new, previously unknown mechanism.
The study opens a new chapter in Alzheimer's research. It suggests that early therapeutic interruption of the amyloid-fibrinogen interaction could mitigate the course of the disease – especially in the early stages, when amyloid deposits are still low, but vascular damage is already present.
Interestingly, the Alzheimer's drug Lecanemab, an already approved antibody medication, targets exactly these complexes. But according to the researchers, this is probably just the beginning. Future therapies could take a more targeted approach and protect both vascular health and neuronal stability.
"Of course, inhibiting this binding would not cure Alzheimer's," says Simões-Pires. "But it could mitigate some of the most harmful processes – and achieve a lot in combination with other approaches."
For longevity research, this discovery is highly relevant. It shows that longevity in the brain is not just a matter of neuronal health – but also of the vessels, barriers, and inflammatory balance. So, if you want to keep your brain young, you also need to pay attention to your heart and circulation.
A healthy blood-brain barrier, stable vessels, and low inflammation levels are not only Alzheimer's prevention but real longevity factors. They remind us that longevity never begins in one organ but in the interplay of all systems – including those that invisibly draw boundaries between blood and consciousness.
Nils Behrens is the Chief Brand Officer of Sunday Natural and host of the podcast HEALTHWISE. The sought-after health expert also lectures as a professor at the Fresenius University of Applied Sciences. Previously, Behrens worked over 12 years as Chief Marketing Officer of the Lanserhof Group and host of the successful "Forever Young" podcast.
