Abstract
INTRODUCTION
Chronic neuroinflammation in Alzheimer’s disease (AD) alters astrocyte physiology and neurovascular unit function. AD patients frequently experience recurrent systemic inflammatory insults from comorbid conditions, which act as “secondary-hits” believed to worsen cognitive decline. The impact of these secondary insults on astrocyte-mediated neurovascular regulation remains unknown.
METHODS
We applied intravital two-photon microscopy to longitudinally investigate astrocytic Ca2
+ dynamics and functional hyperemia during sensory stimulation in APP/PS1dE9 mice before and during secondary lipopolysaccharide (LPS)-induced systemic inflammation.
RESULTS
AD mice exhibited diminished stimulation-evoked astrocytic Ca2
+ activity, while functional hyperemia remained largely preserved. LPS further suppressed astrocytic Ca2
+ responses and produced temporally specific vascular alterations, with AD and wild-type mice following divergent inflammatory trajectories.
DISCUSSION
Our findings provide the first in vivo longitudinal characterization of how secondary systemic inflammation disrupts astrocyte-mediated neurovascular regulation. The selective vulnerability of astrocytic Ca2
+ signaling relative to vascular output implicates recurrent inflammatory insults as a clinically relevant contributor to neurovascular dysfunction in preclinical AD.
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This post is Copyright: | July 23, 2026
Neuro-Dementia