White Blood Cell Mutation May Drive Early Stages Of Dementia

Research into an ultra-rare type of early-onset dementia has uncovered a novel genetic mutation that results in dysfunctional white blood cells and a breakdown of the blood-brain barrier.

A new hypothesis is presented in this study suggests an entirely different mechanism may underpin the neurodegeneration seen in ALSP. Using post-mortem brain tissue samples and pre-clinical models the team of Trinity College researchers discovered certain CSF1R mutations result in abnormal activity in macrophages, a common type of white blood cell.

These dysfunctional white blood cells were found to damage the blood-brain barrier and it is this chain of events that may be driving the progressive neurodegeneration.

“The most exciting aspect of our study is that we have now honed in on a novel pathway that to date has not been explored in great detail,” says first author on the new study, Conor Delaney.

“Additionally, our data suggest that modifying white blood cell function may be therapeutically relevant for progressive neurodegenerative conditions.”

So the researchers suggest this particular finding, focusing on white blood cell dysfunction driving blood-brain barrier damage, may be transferable to Alzheimer’s-related dementias.

A growing body of research has begun to convincingly present strong links between the earliest stages of cognitive decline and the blood-brain barrier breaking down.

A compelling 2018 review article went as far as suggesting a dysfunctional blood-brain barrier could play a part in the earliest stages of many neurological disorders, from Alzheimer’s and Parkinson’s to ALS and multiple sclerosis.

Colin Doherty, another author on the new study, suggests studying these rare, rapidly progressing forms of neurodegenerative disease allows for unique insights into the mechanisms that more slowly play out in common forms of dementia, and this newly discovered mechanism opens the door for entirely novel research pathways.