Clasmatodendrosis and beta-amyloidosis in aging hippocampus

Alterations of the tightly interwoven neuron/astrocyte interactions are frequent traits of aging, but also favor neurodegenerative diseases, such as Alzheimer disease (AD). These alterations reflect impairments of the innate responses to inflammation-related processes, such as beta-amyloid (Ab) 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 fluorescence-lifetime imaging microscopy/phasor multiphoton analysis with confocalmicroscopy, implemented with a novel method to separate spectrally overlapped immunofluorescence and Ab autofluorescence. By comparing data from young control rats, chronically inflamed rats, and old rats, we identified age-specific alterations of neuron/astrocyte interactions in the hippocampus. We found a correlation between Ab aggregation (+300 and +800% of aggregated Ab peptide in chronically inflamed and old vs. control rats, respectively) and fragmentation (clasmatodendrosis) of astrocyte projections (APJs) (+250 and +1300% of APJ fragments in chronically inflamed and old vs. control rats, respectively). Clasmatodendrosis, in aged rats, associates with impairment of astrocyte-mediated Ab clearance (-45% of Ab deposits on APJs, and +33% of Ab deposits on neurons in old vs. chronically inflamed rats). Furthermore, APJ fragments colocalize with Ab deposits and are involved in novel A beta-mediated adhesions between neurons. These data define the effects of Ab deposition on astrocyte/neuron interactions as a key topic in AD biology.-Mercatelli, R., Lana, D., Bucciantini, M., Giovannini, M. G., Cerbai, F., Quercioli, F., Zecchi-Orlandini, S., Delfino, G., Wenk, G. L., Nos, D. Clasmatodendrosis and beta-amyloidosis in aging hippocampus. FASEB J. 30, 1480-1491 (2016). www.fasebj.org