The Most Devastating Symptom Of Alzheimer's Finally Has An Explanation – And, Maybe Soon, A Treatment

One of the most famous symptoms of Alzheimer's – and definitely one of the most devastating – is when patients start to forget their friends, family, and loved ones. Thanks to a new study from researchers at the University of Virginia, though, we may now know why that happens – and perhaps one day, we’ll be able to prevent it.

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“In Alzheimer’s disease, people have trouble remembering their family and friends due to the loss of a memory known as social memory,” explained Lata Chaunsali, a grad student in the University of Virginia's (UVA) School of Medicine and coauthor of the new research, in a statement. 

It’s an effect that starts slow – patients may just mix up names and faces, or misremember past events – but eventually, it always progresses. Patients start to forget things like their address or where they went to high school; it can stop you from understanding simple social cues and communicating with those around you. Maintaining relationships becomes almost impossible as you forget even those most important to you, and the outside world becomes overwhelmingly confusing and unfamiliar.

But despite how major and painful all this evidently is, we so far haven’t really known what’s to blame. Recent work has connected the decline in social memory to changes in the extracellular matrix, or ECM, around regions such as the hippocampus and prefrontal cortex – the molecules that “fill in” the space around cells in the brain, providing structure and support – but how and why those changes would produce cognitive problems has proved elusive.

Now, though, the Virginian researchers have figured it out. It’s linked to the breakdown of a particular kind of structure within the ECM – so-called “perineuronal nets”, or PNNs, that surround specific neurons and help stabilize synapses and “set” memories in our minds.

“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 explained. 

It’s a big find, and not just because it’s new information. “Finding a structural change that explains a specific memory loss in Alzheimer’s is very exciting,” said corresponding author Harald Sontheimer, chair of UVA’s Department of Neuroscience and member of the UVA Brain Institute. And this is “a completely new target,” he added. "[T]he 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 of disease.”

But the best news of all? “We already have suitable drug candidates in hand,” Sontheimer said – specifically, a class of drugs known as “MMP inhibitors”. They’re already being investigated for use in cancer and arthritis treatments, but MMPs – “matrix metalloproteinases”, if you’re feeling multisyllabic – are known to contribute to PNN degradation, so the team decided to try preemptively treating mice with the drugs too. And it worked.

Of course, this is only a first step. Alzheimer’s patients and their families shouldn’t expect to run down to their local CVS and pick up some MMP inhibitors first thing tomorrow. But for the 55 million people globally currently suffering from the disease – and the almost 20 million projected to be diagnosed within the next five years – it’s no doubt cause for optimism.

“Our research will help us get closer to finding a new, non-traditional way to treat or better yet prevent Alzheimer’s disease,” Chaunsali said. “Something that is much needed today.” 

The paper is published in the journal Alzheimer’s and Dementia.