Wasteosomes ( corpora amylacea ) as a hallmark of chronic glymphatic insufficiency

Abstract

In different organs and tissues, the lymphatic system serves as a drainage system for interstitial fluid and is useful for removing substances that would otherwise accumulate in the interstitium. In the brain, which lacks lymphatic circulation, the drainage and cleaning function is performed by the glymphatic system, called so for its dependence on glial cells and its similar function to that of the lymphatic system. In the present article, we define glymphatic insufficiency as the inability of the glymphatic system to properly perform the brain cleaning function. Furthermore, we propose that corpora amylacea or wasteosomes, which are protective structures that act as waste containers and accumulate waste products, are, in fact, a manifestation of chronic glymphatic insufficiency. Assuming this premise, we provide an explanation that coherently links the formation, distribution, structure, and function of these bodies in the human brain. Moreover, we open up new perspectives in the study of the glymphatic system since wasteosomes can provide information about which variables have the greatest impact on the glymphatic system and which diseases occur with chronic glymphatic insufficiency. For example, based on the presence of wasteosomes, it seems that aging, sleep disorders, and cerebrovascular pathologies have the highest impact on the glymphatic system, whereas neurodegenerative diseases have a more limited impact. Furthermore, as glymphatic insufficiency is a risk factor for neurodegenerative diseases, information provided by wasteosomes could help to define the strategies and actions that can prevent glymphatic disruptions, thus limiting the risk of developing neurodegenerative diseases.

Corpora amylacea negatively correlate with hippocampal tau pathology in Alzheimer’s disease

“…For example, CA have been shown to contain ubiquitin, providing evidence that they may interact with the UPS, but more research is needed to elucidate their relationship ( Augé et al, 2018 ). Additionally, the glymphatic system may be associated with the extrusion of CA, since CA are thought to be a hallmark of chronic glymphatic insufficiency ( Riba et al, 2022b ). It is likely these waste clearance mechanisms work together to identify, sequester, and clean the brain from pathological debris, and in proteinopathies such as AD, their proper functioning is essential to prevent or delay disease progression.…”

“…An alternative to the clearance of tau through the glymphatic system is corpora amylacea (CA)-mediated waste clearance, a mechanism present in the central nervous system and other tissues. CA, also known as wasteosomes ( Riba et al, 2022a , b , 2023 ), have recently been linked to the glymphatic system ( Riba et al, 2022b ). CA are granular bodies ranging from 10 to 50 μm that accumulate waste products throughout the brain ( Cavanagh, 1999 ; Navarro et al, 2018 ; Riba et al, 2019 ).…”

Distribution of corpora amylacea in the human midbrain: using synchrotron radiation phase-contrast microtomography, high-field magnetic resonance imaging, and histology

“…Although we found that these CA make up only 2 percent of its entire population in our brain stem samples, it is worth noting that certain vessels tend to accumulate CA throughout a long trajectory ( Figure 5D , Supplementary Figures 12 – 16 ). Riba et al ( 2022 ) recently suggested the accumulation of CA as a sign for failure the of glymphatic system to remove waste. According to this theory, accumulation of CA should occur predominantly in perivenous spaces rather than in periarterial spaces.…”

New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease

“…Modulation of brain fluid transport may be a novel target for developing new drugs to fight acute and chronic inflammation in the brain. There is evidence that the presence of increased wasteosomes (or corpora amylacea i.e., amyloid bodies) is an indicator of chronic failure of the GS activity [ 151 ]. Chronic lymphatic insufficiency is a risk factor for NDDs, and thus, improvement of the GS is a novel target of AD drug strategies.…”