[P1–183]: LOSS OF CLUSTERIN SHIFTS AMYLOID DEPOSITION TO THE CEREBROVASCULATURE VIA DISRUPTION OF PERIVASCULAR DRAINAGE PATHWAYS

• DOI: 10.1016/j.jalz.2017.06.250
• Publication Date: 2017-10-20T08:46:22Z
• Authors: Aleksandra Wojtas; Silvia S. Kang; Guojun Bu; Roxana O. Carare; John D. Fryer
• Keywords: Clusterin; Parenchyma; Ex vivo; Amyloid beta; Amyloid (mycology)

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide deposition in brain parenchyma as plaques and cerebral blood vessels amyloid angiopathy (CAA). CAA leads to several clinical complications, including intracerebral hemorrhage. The underlying molecular mechanisms that regulate plaque the vast majority of sporadic AD patients remain unclear. clusterin (CLU) gene genetically associated with CLU has been shown alter aggregation, toxicity blood-brain barrier transport Aβ, suggesting it might play a key role regulating balance between Aβ clearance both vessels. Here, we investigated effect on pathology using APP/PS1 mouse model amyloidosis Clu+/+ or Clu-/- background. We measured pathology, neuritic dystrophy, microhemorrhage, neuroinflammation. also performed perivascular experiments ex vivo vessel binding assays. found marked decrease but an equally striking increase within cerebrovasculature APP/PS1; mice. Surprisingly, despite several-fold levels, mice had significantly less hemorrhage inflammation. impaired exogenously added prevented isolated vivo. These findings indicate absence CLU, shifts drainage pathways resulting fewer parenchymal more due loss chaperone activity, complicating potential therapeutic targeting for AD.