Alzheimer’s disease is a form of brain decline that affects millions across the world. The exact cause is unclear, but new research is uncovering the factors that allow Alzheimer’s to become established in the brain.

Which brain cells are the most vulnerable to Alzheimer’s?

In Alzheimer’s disease, as in other forms of dementia, a defining feature is the accumulation of certain toxic proteins in the brain.  These toxic proteins form plaques that disrupt the communication between brain cells, intensifying problems with thinking, judgement and memory.  Most researchers point to a particular protein – beta-amyloid – as the main protein in plaque development and brain function decline.

However, more and more, researchers are finding that another protein – tau – is just as important.  In a new study, researchers found that tau accumulates to form plaques around a specific type of brain cell.  In addition, the investigators were also able to reveal that people with a certain genetic profile may be prone to tau plaques.  The researchers reported their findings in a paper recently published in Nature Neuroscience.

As a basis for reviewing this new study it is importing to know that the brain contains different types of cells. The two most important are neurons and glial cells.  Neurons communicate information and play a key role in thinking function.  Glial cells have several roles, including supporting and protecting neurons and the connections between them.  Neurons fall into two categories: excitatory, which trigger electrical impulses, and inhibitory, which balance out the activity of excitatory neurons.

The researchers specifically studied tau protein accumulation in a mouse model, and in the brains of people who have received Alzheimer’s diagnoses.  The study found that excitatory neurons were those most exposed to the disruptive effect of the tau protein.

The defining features that make a neuron most vulnerable seems to be their shape (morphology) and location.  Neurons located in two parts of the brain – entorhinal cortex and hippocampus – seem to be most impacted. 

Following this finding, the researchers compiled genetic analyses based on the data of people who did not have either Alzheimer’s disease or any other neurological issues.  The investigators noticed some important genetic differences between the excitatory and inhibitory neurons, which could explain why the excitatory neurons are more susceptible to tau aggregation. 

Specifically, the researchers found that one gene – BAG3 – regulates the clearance of tau protein in the brain.   BAG3 activity was much higher in neuron cells than in non-neuronal cells.  Among neurons, BAG3 was highest in inhibitory neurons.  This suggests an explanation for inhibitory neurons’ reduced vulnerability to tau plaques and excitatory neurons’ increased susceptibility to toxic plaque formation.

This study would encourage future research to focus on how interactions between certain genes could influence Alzheimer’s and enhance brain cells’ vulnerability to toxic plaques.