Why Alzheimer's patients stop recognizing their loved ones

Few moments are more painful than the day a loved one with Alzheimer’s no longer recognizes you. 

A new study from the University of Virginia (UVA) offers a concrete, testable reason why that happens, and a possible way to slow or prevent it.

UVA neuroscientist Harald Sontheimer, graduate student Lata Chaunsali, and colleagues report that damage to protective “perineuronal nets” around brain cells may strip away social memory.

In mice, keeping those nets intact helped the animals remember one another.

“Finding a structural change that explains a specific memory loss in Alzheimer’s is very exciting,” Sontheimer said. “It is a completely new target, and we already have suitable drug candidates in hand.”

Hidden scaffolds help us remember

Perineuronal nets are mesh-like sheaths of proteins and sugars that wrap certain neurons. Think of them as scaffolding and shielding at once. They stabilize connections, regulate signaling, and help lock in learned information. 

Sontheimer’s team has been piecing together their role for years. The new work builds on that foundation: if the nets fray, memory suffers – but not all memories in the same way.

In mouse experiments, the researchers selectively weakened these nets. The animals could still learn new things and tell familiar objects from new ones. But they failed at a different task: recognizing another mouse they had already met.

That pattern matches a common arc in people with Alzheimer’s. Names and faces slip first. Objects and places fade later.

Rising global burden of Alzheimer’s

Timing matters. Alzheimer’s currently affects about 55 million people worldwide, with cases projected to surge by more than a third in just five years.

UVA has launched the Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases to translate ideas from the lab to the real world.

This nets-based line of research slots directly into that mission, because it points to therapies beyond the traditional focus on amyloid plaques.

Strikingly, the team observed that net loss occurred without any dependence on plaque biology. That suggests a parallel pathway of damage.

The discovery also opens a door for combination strategies that don’t live or die by the success of anti-amyloid drugs alone.

Can we protect the nets?

The group tested a straightforward idea: if enzymes contribute to net breakdown, can enzyme blockers slow the process?

Experts gave mice matrix metalloproteinase (MMP) inhibitors – drugs already under study for cancer and arthritis.

The result was encouraging. The treatment preserved perineuronal nets and helped the mice keep social memories.

“In our research with mice, when we kept these brain structures safe early in life, the mice suffering from this disease were better at remembering their social interactions,” Chaunsali said. 

“Our research will help us get closer to finding a new, nontraditional way to treat or, better yet, prevent Alzheimer’s disease, something that is much needed today.”

What this could mean for families

Targeting nets reframes a symptom that hits families hardest – loss of recognition – as something rooted in tangible brain architecture. That makes it a tractable engineering problem, not just a tragic mystery. 

If clinicians can preserve these structures early, they might delay the point at which social memory falters. That would not cure Alzheimer’s. But it could buy time for relationships, routines, and caregiving plans to hold.

“Although we have drugs that can delay the loss of perineuronal nets, and thereby delay memory loss in disease, more research needs to be done regarding safety and effectiveness of our approach before this can be considered in humans,” Sontheimer said.

Safety is a real question. MMPs do many jobs in the body, from wound healing to remodeling tissues. Inhibiting them broadly could bring side effects. 

The good news is that net biology also offers other levers, such as tweaking net composition, dialing down overactive microglia, or bolstering the neurons most dependent on net support.

The path to patients will likely involve targeted delivery, careful dosing, and smart trial design focused on early stage disease.

A broader picture of Alzheimer’s

The findings also challenge a narrow view of what drives the disease.

“One of the most interesting aspects of our research is the fact that the loss of perineuronal nets observed in our studies occurred completely independent of amyloid and plaque pathology, adding to the suspicion that those protein aggregates may not be causal to the disease,” Sontheimer explained.

That doesn’t absolve amyloid of all blame. It does argue that we need a wider toolbox, and a readiness to treat multiple mechanisms at once.

The next steps

The team’s roadmap is clear. First, replicate the results across additional Alzheimer’s models, ages, and brain regions.

Second, map precisely which neurons rely most on nets for social memory, and when they’re most vulnerable.

Third, test safer, more selective ways to protect or rebuild nets, ideally with drugs that cross the blood-brain barrier and spare healthy remodeling elsewhere in the body.

Lastly, build biomarkers – imaging or fluid tests – that can flag net degradation early in people.

If those pieces come together, clinicians could one day pair an early diagnostic with a nets-preserving therapy aimed not just at slowing cognitive decline, but at keeping recognition alive for longer.

That would be a genuine change in what the disease takes away, and when.

The study is published in the journal Alzheimer’s & Dementia.

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