Abstract Details

Title Neuroprotection of HP-beta-CD in the adult transgenic mice of Alzheimer disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-003

Objective To further investigate neuroprotection of a non-toxic compound Cyclodextrin in a mouse model of AD.

Background

Alzheimer disease (AD) is the most common neurodegenerative disease, and its prevalence increases exponentially with advancing age. Both a better understanding of the pathogenesis of dementing illnesses, as well as effective therapies targeting the underlying pathogenic mechanisms of AD are critically needed. Epidemiologic studies have shown that cholesterol is a major risk factor for AD. There is also biological evidence indicating that lipid metabolism plays a key role in AD pathogenesis. Cyclodextrin (CD) is a non-toxic compound that reduces cholesterol levels and exerts neuroprotection in animal models of Niemann Pick disease type C-1 (NPC-1) and AD.

Design/Methods

An experimental study in Tg19959 mouse model.

Results Despite promising results previousl published in Journal of Experimental Medicine, the effects of HP-β-CD in adult mice with mature blood-brain barrier (BBB) are unknown. To investigate the effects of HP-β-CD in adult mice, we treated Tg19959 mice at 4 mons of age with HP-β-CD for 7 days and 2 months. Comparing to Tg19959 mice treated with saline, we observed a trend of reduced amyloid plaques in the brain of Tg19959 mice treated with HP-β-CD in both groups of 7 days and 2 months treatment; a significant reduction of fibrillar amyloid aggregates positive to antibody OC, and a significant reduction of amyloid oligomers positive to antibody A11 (n=5 each group) in the group of 2 months treatment.

Conclusions

Our previous study showed that long term treatment of HP-β-CD in young mice prevents neurodegeneration. The current study further demonstrate that CDs exert protection in adults Tg19959 mice with mature BBB.

Considering the oligomers and soluble fibrillars might be more toxic to neuronal functions, these findings are very interesting in understanding the mechanisms of CDs exerting protection in AD pathogenesis

Authors/Disclosures
Jiaqi Yao, MD (Baylor Scott and White) PRESENTER	Dr. Yao has nothing to disclose.
	No disclosure on file
Paisith Piriyawat, MD (Texas Tech University)	Dr. Piriyawat has nothing to disclose.
M. F. Beal, MD (Cornell Medical Center)	No disclosure on file
Salvador Cruz-Flores, MD, FAAN (Paul L. Foster School of Medicine Texas Tech University Health Sciences Center)	The institution of Dr. Cruz-Flores has received research support from University of Texas System.

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