Task Impact of Space-Radiation Induced Alterations on Toxic Protein Accumulation Associated with Neurodegenerative Disease (Completed)
Last Published:  07/29/22 01:33:24 PM (Central)
Short Title: Toxic Protein Neurodegenerative
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):

Aim 1: Assess the role of LRP1 at the BBB on Aβ clearance at different radiation doses and post-exposure durations in WT mice using established tracer techniques. LRP1 expression levels in brain microvessels and parenchyma will be determined and correlated with Aβ clearance.


Aim 2: Evaluate the role of the glymphatic system in radiation induced accumulation of brain Aβ, and inulin, an ISF flow marker, at different radiation doses and post-exposure durations in wild-type (WT) mice. Alterations in ISF flow will be correlated with measures of astrocyte activation and



Aim 3: Determine the effects of radiation on the proliferative capacity of microglia during normal response to injury in WT mice, and for the ability of microglia to phagocytize Aβ in vivo using APP/PS1 mice. Alterations will be correlated with measures of neuroinflammation and evidence of microglial phenotypic changes, including senescence.


Aim 4: Establish mechanisms linking cellular changes to Aβ accumulation, we will attempt to reduce radiation-associated effects on AD pathology and cognition using a radio-protective and anti-inflammatory drug that also enhances Aβ clearance from the brain.

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