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Alzheimer’s Disease

Alzheimer’s Disease. Discovery. 1901 Dr. Alois Alzheimer Auguste Frau (died in 1906) Alzheimer found - shrunken brain - unique microscopic deposits. Quick Facts. One out of Seven 71+ has dementia 70% of dementia is Alzheimer’s 5 million Americans

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Alzheimer’s Disease

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  1. Alzheimer’s Disease

  2. Discovery • 1901 • Dr. Alois Alzheimer • Auguste Frau (died in 1906) • Alzheimer found - shrunken brain - unique microscopic deposits

  3. Quick Facts • One out of Seven 71+ has dementia • 70% of dementia is Alzheimer’s • 5 million Americans • 20 million worldwide • Direct and indirect costs of dementia = $148 billion annually • No cure • Average life expectancy is 8 years past onset of AD

  4. Seven Stages of AD • Normal function • Very mild cognitive decline • Mild cognitive decline • Moderate cognitive decline • Moderately severe cognitive decline • Severe cognitive decline • Very severe cognitive decline

  5. Diagnosing AD • No concrete diagnostic tool • Main symptom is deteriorating short term memory • Accurate 90% of the time - physical exams - blood and urine samples - PET scans - structured interviews

  6. Changes in the Brain • Decrease in size and activity • Build up of plaques • Masses of neurofibrillary tangles

  7. Changes in Size and Activity • Dramatically smaller brain • Much less brain activity • Hippocampus severely deteriorated

  8. Plaques • Amyloid plaques • Collection of Aβ peptide • Cleaved from Amyloid Precursor Protein (APP) • β-secretase cleaves at the N-terminus → APPsb and c99 • C99 cleaved by γ-secretase→ Aβ peptide and a p3 peptide

  9. Neurofibrillary Tangles (NFT) • Built by paired helical filaments (PHF) • Tau is the main protein in PHF • Abnormally phosphorylated in AD patients • Tau protein kinases I and II phosphorylate tau • Abnormal tau collects as NFT

  10. Other AD Factors • Amyloid-derived diffusible ligands (ADDLs) • Free-radicals • Chronic inflammation

  11. Treatment • No cure • Acetylcholineasterase inhibitors - Donepezil - Rivastigmine - Glantamine - Increase the amount of neurotransmitters in the synaptic cleft • Memantine: inhibits the NMDA receptor for clearer thinking

  12. The search for a cure… • Prevent the toxic intermediates from forming during amyloid aggregation • Inhibit Aβ peptide metabolism. • Find an effective means of reducing oxidative stress and inflammation • Treat the plaques and NFT

  13. In Conclusion • This is a terrible disease • Current treatment plans are not nearly effective enough • It is a problem that will continue to grow

  14. Sources • http://www.drugdevelopment-technology.com/projects/flurizan/flurizan5.html • http://www.bioscience.org/news/scientis/alzheim1.htm • http://www.photonics.com/content/news/2007/April/4/87093.aspx • http://www.smh.com.au/news/health/pills-in-poop-is-the-scoop/2007/11/14/1194766740042.html • www.alz.org • http://www.templateswise.com/detail/link-56.html • www.robertocampus.com • www.northwestern.edu • http://abcnews.go.com/Technology/story?id=1831398&page=1

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