Title : Implications for Serum Amyloid P in the Pathogenesis of Alzheimer’s Disease
Serum amyloid P component (SAP) is found in all amyloids and studies have suggested that it plays an integral role in the formation, progression, and maintenance of the disease processes. The mouse SAP (mSAP) does not interact with human proteins and since most of the models for Alzheimer’s disease (AD), tau pathology, etc. are with human cDNAs/genes, mSAP does not associate with human aggregates and fibrils. SAP regulates inflammation, and inflammatory signaling pathways impair cognitive function in vivo. The biological impact of SAP in AD is not well characterized. Our long-term goal is to determine the mechanisms regulating SAP function, particularly within the setting of AD. The objective of this grant is to characterize the role for SAP in AD. Recent studies from our laboratory and others have provided information for the role of SAP in AD progression: 1) SAP levels are increased in mouse models of inflammation and AD; 2) in humans, SAP is present in the brains of patients with AD and found in the plaques and tangles; 3) SAP stabilizes amyloid fibrils; 4) SAP deficient mice have altered AA amyloid; 5) in human SAP transgenic mice, SAP is associated with Ab plaques and cerebral amyloid angiopathy (CAA). The central hypothesis is that SAP facilitates AD pathogenesis, via enhancing inflammatory responses, expedites amyloidogenesis (oligomerization), and contributes to disease progression by functioning as a chaperone. This contribution is significant since it will establish that targeting of SAP by therapies have the potential to regulate inflammatory activity through molecular mechanisms. These studies will hopefully provide potential targets for therapeutic intervention in neurological disorders. The proposed research is innovative because we investigate the effect of inflammatory signaling pathways on SAP in neurological diseases, a heretofore-unexamined process.
What will audience learn from your presentation?
- Will help understand the implications in AD.
- Provide information on potential targets for therapeutic intervention.
- Will provide a better understanding of the disease process.