Wasteosomes as a Marker for Age-Related Impairment of Cerebrospinal Fluid Drainage

There is a growing awareness that removal of metabolic waste from the brain is impaired with age, and that this contributes to the onset of neurodegenerative conditions characterized by rising levels of protein aggregates of various sorts in the brain. All of that waste might be better removed from the brain were paths through the cribriform plate and glymphatic system maintained at youthful efficiency. Leucadia Therapeutics is working on a safe way to open a new passage through the cribriform plate, but the glymphatic system is a more challenging prospect. It isn't fully understood how best to intervene in what is most likely a multifaceted degeneration connected to most or all of the fundamental mechanisms of aging.

The glymphatic system is responsible for clearing the brain parenchyma. To date, the terms glymphatic system failure or glymphatic system dysfunction have been used to define its malfunction. In a new paper, the concept of glymphatic insufficiency is defined as the inability of the glymphatic system to properly perform the brain's cleaning function. This makes it possible to describe that the failure can be acute or chronic, depending on the duration of the process, and to specify that the failure can be caused by a failure of the glymphatic system itself or by an overproduction of waste substances that exceeds the clearing capacity of this system.

The wasteosomes or amylase bodies of the human brain were first described in 1837. Researchers have shown that amylase bodies act as containers for waste substances from the brain and can be expelled by astrocytes into the cerebrospinal fluid. A new paper now provides evidence that increased wasteosomes or starch bodies in the human brain are a manifestation of chronic glymphatic system insufficiency. The first indication of this relationship is that most factors that are associated with large amounts of wasteosomes, such as ageing, certain cardiovascular disorders, and poor sleep quality, are also associated with disruptions of the glymphatic system.

The study also mentions several elements and evidence that suggest that chronic lymphatic insufficiency is a risk factor for neurodegenerative diseases, especially neurodegenerative diseases that involve the aggregation of certain fibrillar proteins, such as β-amyloid protein in Alzheimer's disease, phosphorylated tau in frontotemporal dementia and Alzheimer's disease, or α-synuclein in Parkinson's disease. "In case of lymphatic insufficiency, the elimination of these proteins is restricted, and all indications are that this contributes to the development of these diseases."

Link: https://www.eurekalert.org/news-releases/972882


Speaking of Leucadia Therapeutics, any word on a clinical trial? Their website mentioned something beginning in 2022.

Posted by: Gregory Schulte at December 7th, 2022 12:04 PM
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