A-beta-induced distress of astrocytes triggers Alzheimer disease pathology through non-canonical delta secretase activity
Willnow, T.; Schmidt, V.; Malik, A.; Ziemlinska, E.; Obrebski, T.; Zurawska-Plaksej, E.; Cendrowski, J.; Hempstead, B. L.
Show abstract
The importance of astrocytes for Alzheimer disease (AD) pathology is increasingly appreciated, yet the mechanisms whereby this cell type impacts neurodegenerative processes remain elusive. In a genetic mouse model with diminished astrocyte stress response, even low levels of amyloid-{beta} trigger astrocyte reactivity, resulting in brain inflammation and massive amyloid and tau pathologies. This dysfunctional response of astrocytes to amyloid-{beta} acts through activation of {delta} secretase, a stress-induced protease implicated in both amyloid and tau-related proteolytic processing. Our findings identify a failed astrocyte stress response to amyloid-{beta} as an early inducer of amyloid and tau co-morbidity, a noxious process in AD acting through a unique non-canonical secretase pathway.
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