WASTEOSOME BURDEN IN THE HUMAN BRAIN SUGGESTS CHRONIC GLYMPHATIC INSUFFICIENCY IN NEURODEGENERATIVE DISEASES

The glymphatic system is essential for brain waste clearance and the maintenance of cerebral homeostasis. Impairment of this system has been proposed to be associated with pathological processes that contribute to the progression of brain disorders, including neurodegenerative diseases characterized by protein misfolding and aggregation.
Taking into consideration that wasteosomes (corpora amylacea) are brain structures involved in waste sequestration and are known to increase under conditions of chronic glymphatic insufficiency, in this study, we investigated whether the accumulation and distribution of wasteosomes in certain neurodegenerative diseases supports the presence of chronic glymphatic insufficiency.
Post-mortem human brain tissue from 185 donors was analysed, including cases of Alzheimer’s disease, amyotrophic lateral sclerosis with TDP-43 proteinopathy, frontotemporal lobar degeneration with TDP-43 or tau pathology, and non-diseased controls. Wasteosomes were systematically assessed in 28 regions across five major brain areas using region-specific scoring methods. Statistical analyses included variance and covariance models, complemented by decision tree approaches.
Results reveal a predominant accumulation of wasteosomes in seven specific brain regions. These regions did not correspond to the main areas of pathology for each disease, but were all associated with glymphatic drainage pathways. Notably, all neurodegenerative disease groups exhibited significantly higher wasteosome loads in these regions compared with controls.
These findings support the presence of chronic glymphatic insufficiency as a shared feature across multiple neurodegenerative conditions. Furthermore, wasteosome burden and distribution may provide valuable insights into glymphatic impairment and its potential contribution to neurodegeneration.