CD44-POSITIVE ASTROCYTES ARE THE ASTROCYTES INVOLVED IN WASTEOSOME (CORPORA AMYLACEA) FORMATION AND THEIR RELEASE INTO THE CEREBROSPINAL FLUID

Wasteosomes, also known as corpora amylacea, are spherical polyglucosan bodies that accumulate in the periventricular, perivascular and subpial regions of the human brain, particularly during aging and in several neurodegenerative diseases. Wasteosomes are originated in astrocytes, and recent research suggests that they act as waste containers and can be released into the cerebrospinal fluid.
In this study, we hypothesised that CD44-positive astrocytes are those harbouring wasteosomes. Brain tissue samples from 20 individuals, including patients with different neurodegenerative diseases as well as non-diseased controls, were analysed. Immunohistochemistry and immunofluorescence were performed using antibodies against GFAP to identify astrocytes, CD44 to label interlaminar astrocytes, and p62 as a specific marker for wasteosomes.
Across multiple brain regions, wasteosomes were exclusively observed in areas populated by CD44-positive astrocytes. GFAP-positive astrocytic filaments were detected between wasteosomes and the CD44 membrane receptor, supporting the intra-astrocytic localization of these structures. In addition, some wasteosomes located in the subarachnoid space displayed CD44 remnants adherent to their surface, suggesting that CD44-positive astrocytes are those releasing wasteosomes into the cerebrospinal fluid.
These findings identify CD44-positive astrocytes as the principal cellular niche for wasteosomes and point to a potential role of CD44 in wasteosome biogenesis and extrusion. Further studies are required to elucidate the functional significance of this relationship and its possible implications in neuropathological conditions.