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Lecture+18+Alzheimers2 - Current Treatment of AD...

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1 Current Treatment of AD Cholinergic therapy Brain acetylcholine is reduced Inhibit cholinesterase enzyme Multiple drugs work on this principle - Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) NMDA receptors Glutamine - excitatory neurotransmitter, stimulates NMDA receptors Glutamate-excitotoxicity thought to play a role in neurodegeneration Memantine (Namenda) - NMDA Receptor antagonist None of these drugs are very effective: Minor symptomatic improvement Donepezil (Aricept) – Pivotal Clinical Trial -4 -3 -2 -1 0 1 2 3 0 6 12 18 24 30 Weeks of Drug Treatment Mean Change from Baseline ADAS-Cog Rating 10 mg/day 5 mg/day Placebo Clinical Improvement Clinical Decline Withdrawal phase
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2 β secretase γ secretase Amyloid A β Soluble Oligomeric Amyloid Aggregated Fibrillar Amyoid Plaque Amyloid Inflammation Secretase Inhibitors X X X Anti-Aggregation X Immunization Clearance Anti-Inflammatory X X X X Immunization for Alzheimer’s Disease Human mutant APP gene (V717F) Immunization begun at 6 weeks with A β No amyloid plaques Sham/control immunizations Transgenic mouse amyloid plaques
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