Harvard study makes new discovery about frontotemporal dementia

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Dementia encompasses a range of neurodegenerative conditions that lead to memory loss and cognitive deficiencies and affect some 55 million people worldwide.

Yet despite its prevalence, there are few effective treatments, in part because scientists still don’t understand how exactly dementia arises on a cellular and molecular level.

In a study from Harvard, scientists have made progress in unraveling the mechanism underlying a type of dementia that strikes early in life.

They discovered that a genetic form of frontotemporal dementia (FTD) is linked to an accumulation of specific lipids in the brain—and this accumulation results from a protein deficiency that interferes with cell metabolism.

The results, based on experiments in human brain cells and in animal models, provide new insights into FTD that could inform the design of new therapies.

Additionally, the findings highlight a mechanism of metabolic disruption that may be relevant in other forms of neurodegeneration.

Previous studies have linked progranulin to parts of the cell called lysosomes, which are responsible for cleanup and other metabolic activities in cells.

The researchers initially found that progranulin-deficient human cell lines and mouse brains, as well as brain cells from patients with FTD, had an accumulation of gangliosides—lipids commonly found throughout the nervous system.

Next, the team analyzed the types and amounts of proteins and lipids present inside them. Using this technique, and they found that lysosomes in these cells and tissues from brains with FTD had reduced levels of progranulin, as well as lower-than-normal levels of a lipid called BMP, which is required to break down gangliosides, the lipids commonly found in the central nervous system.

However, when researchers added BMP to cells, they observed that these cells accumulated far lower levels of gangliosides.

Together, the findings suggest that progranulin in lysosomes helps maintain the BMP levels needed to prevent gangliosides from accumulating in brain cells—a buildup that may contribute to FTD.

Moreover, it may be possible to develop therapies that focus on replacing BMP rather than progranulin, he said, and thus target a different part of the mechanism.

The researchers also think that a similar lysosome-based mechanism could be relevant for neurodegenerative diseases beyond FTD—an idea that they note is rapidly gaining ground in the field.

If you care about dementia, please read studies about how the Mediterranean diet could protect your brain health, and Vitamin B supplements could help reduce dementia risk.

For more information on brain health, please see recent studies about factors that have the biggest impact on your dementia risk, and these antioxidants could help reduce dementia risk.

The study was conducted by Wade Harper et al and published in Nature Communications.

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