Clasmatodendrosis and β-amyloidosis in Aging Hippocampus

Alterations of the tightly interwoven neuron/astrocyte interactions are frequent traits of aging, but also favor neurodegenerative diseases, as Alzheimer's disease (AD). These alterations reflect impairments of the innate responses to inflammation-related processes, such as β-amyloid (Aβ)-burdening. Multidisciplinary studies, spanning from the tissue to the molecular level, are needed to assess how neuron/astrocyte interactions are influenced by aging. Our study addressed this requirement by joining FLIM/Phasor multiphoton with confocal microscopy, implemented with a novel method to separate spectrally overlapped immunofluorescence and Aβ-autofluorescence. By comparing data from young control and chronic-inflamed with old rats, we identified age-specific alterations of neuron/astrocyte interactions in the hippocampus. We found a correlation between Aβ-aggregation (+300% and +800% of aggregated Aβ-peptide in chronic-inflamed and old vs control rats, respectively) and fragmentation (clasmatodendrosis) of astrocyte processes (APJs; +250% and +1300% of APJ-fragments in chronic-inflamed and old vs control rats, respectively). Clasmatodendrosis, in aged rats, associates with impairment of astrocyte-mediated Aβ-clearance (-45% of Aβ-deposits on APJs, and +33% of Aβ-deposits on neurons in old vs chronic-inflamed rats). Furthermore, APJ-fragments colocalize with Aβ-deposits, and are involved in novel Aβ-mediated adhesions between neurons. These data define the effects of Aβ-deposition on astrocyte/neuron interactions as a key topic in AD biology.