Alzheimer’s: a map, a path, a clue to a cure

It has been over 100 years since Alzheimer’s disease was first observed; yet it still accounts for hundreds of thousands of deaths worldwide every year, and is the most common form of dementia. Considering how long we have known about it, the information we have is incredibly limited; so how is it caused, why does it develop, and can we treat it?  

New research has recently caused a blossoming of excitement in the neuroscience world, as it could set us on a new path towards answering these all-important questions. First, let’s rewind and find out what we already know about Alzheimer’s Disease…  

These proteins [Beta-amyloids and Tau] cause damage to surrounding neurons which is what causes cell death and ultimately the loss of many brain functions

In 1906, a doctor called Alois Alzheimer was on a mission to improve our understanding of psychiatric disorders. Whilst studying the brain cells of a patient, he found weird clumps and stringy-like structures, which soon became the hallmarks of the disease now termed (surprise surprise) Alzheimer’s.  Fast forward 80 years, and scientists had finally worked out that these odd structures are proteins called Beta-Amyloids (that form the clumps) and Tau (making the strings). We now believe these proteins cause damage to surrounding neurons, which is what causes cell death and ultimately the loss of many brain functions.  

Unlike other parts of our bodies, such as skin cells that replenish every month or so, it is incredibly difficult to regrow and repair brain cells. This is why brain related diseases are particularly devastating, as the body cannot be trusted to mend itself like it would for a normal disease. Discovering that Alzheimer’s Amyloid and Tau formations damage brain cells is all well and good, but if we are going to prevent it, we need to know how, which formations, and where they act.  

To start answering these we need a new tool … Enter: the brain atlas.  

In biology classrooms around the world, students are taught to think of the brain as a series of pathways, where your thoughts, emotions and actions are all terminal points on a path through the vibrant city in the brain. It makes sense that neuroscientists have decided to create maps to help us navigate them in the form of “brain atlases”. Coherently, they do what they say on the tin and map each cell in the brain (or the specific area in question).  

[The brain atlas] uncovered two cell types specifically affected by Alzheimer’s

2.3 million cells, from over 400 pre-frontal cortexes (the part of our brain’s decision-making and other high functions), were examined, identified and mapped in a recent investigation published in Cell. This not only created the largest brain atlas to date, but also uncovered two cell types specifically affected by Alzheimer’s. By comparing healthy and Alzheimer’s-affected atlases they identified two cell types that Alzheimer’s severely depopulates. It not only tells us that Alzheimer’s is good at attacking these cells, but that they play key roles in the brain’s higher functions, which can also be affected by Alzheimer’s, such as memory.  Using genetic studies, they discovered that these cells either produced a hormone called somatostatin, or a protein called reelin. We already know some of the many roles that somatostatin and reelin play in the body, from regulating digestion to aiding adolescent brain development. But neither have an obvious role so far in supporting higher brain functions.  

We still have a long way to go before we fully understand this disease. But, with this huge brain atlas data available to scientists across the world and two distinct cell types to focus in on, this study could bring us a step closer to treating one of the most devastating diseases of our time… hopefully without waiting another 100 years.   

Further information: 

The paper publication in cell: Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer’s disease pathology: Cell 

Article on the research in Nature: The brain cells linked to protection against dementia (nature.com) 

History of Alzheimer’s: The History of Alzheimer’s Disease | BrightFocus Foundation