1. Emerging Treatments in Alzheimer’s Disease
Abby Harrelson
Advisor: Sheldon Kopperl

2. Overview Background Pathology of Alzheimer’s Disease Diagnosis
Current Treatments
Newer therapies

3. Background of AD
Prevalence in United States
Risk factors
Diagnosis

4. Brain Scan Images

5. Pathology Three pathways Aggregation of protein Severe neuronal death
tau protein
amyloid-β 42 peptide
Severe neuronal death

6. Current Treatments Cholinesterase inhibitors
used in mild to moderate cases
Donepezil (Aricept)
N-methyl-D-aspartate receptor antagonist
used in moderate to severe cases
Memantine (Namenda)

7. New Targets Selective inhibitors Enzyme therapy Antioxidants Hormones
Antidepressants
Immunotherapy
Antiviral agents
Allopregnanolone
Combined therapies

8. Selective Inhibitors Selective inhibitors of acetyl cholinesterase
3 binding sites
Aromatic gorge
Active site
Esteratic or anionic site
Anionic site most promising binding site for treatment options

9. Antioxidants Studied as preventative therapy Dietary Options:
Folate supplementation
Vitamins C and E
Pharmaceutical Options:
Mitochondrial antioxidants
CoQ10 vs. MitoQ

10. Hormones Increased incidence of AD in females
Direct link been found between AD and luteinizing hormone
Leuprolide acetate

11. Immunotherapy Amyloid- (A) immunotherapy
Anti-inflammatory interleukin-4
Trial done on mice
Found that IL-4 stimulated neurogenesis

12. Antiviral Agents Herpes simplex virus 1
Causes herpes simplex encephalitis, impacts same part of brain as Alzheimer’s
Antiviral to treat AD
Antiviral agents target viral DNA replication
Determined tau formation dependent on this process
Tested 3, all inhibited tau formation

13. Allopregnanolone
Metabolite of progesterone and a modulator of GABA receptors
Most affective at earliest stages of disease
The appearance of Aβ plaques coincides with end of efficacy

14. Combined Therapies Donepezil + natural hirudin Donepezil + Memantine
Combined treatment showed significant decrease in ADAS-cog score
Donepezil + Memantine
Combined treatment did not show significant decrease in ADAS-cog score

15. Summary Several new treatments have promising outlooks
Need further research
Clinical trials: combined therapy
Easier diagnosis and treatment of prodromal AD

16. Primary References
Svedruzic Z, Popovic K, Smoljan I, Sendula-Jengic V Modulation of -secretase activity by multiple enzyme-substrate interactions: implications in pathogenesis of Alzheimer’s disease. PLoS ONE. 7:3.
Li DQ, Zhou YP, Yang H Donepezil combined with natural hirudin improves the clinical symptoms of patients with mild-to- moderate Alzheimer’s disease: a 20-week open-label pilot study. Int J Med Sci. 9(3):
Chen S, Wang J, Irwin R, Yao J, Liu L, Brinton R Allopregnanolone promotes regeneration and reduces -amyloid burden in a preclinical model of Alzheimer’s disease. PLoS ONE. 6(8):e24293.
Wozniak M, Front A, Preston C, Itzhaki R Antivirals reduce the formation of key Alzheimer’s disease molecules in cell cultures acutely infected with herpes simplex virus type 1. PLoS ONE. 6(10):e25152.
Howard R, et al Donepezil and memantine for moderate- to-severe Alzheimer’s disease. N Engl J Med. 366: