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Alzheimer's Disease (AD)
- Type of dementia characterized by progressive neurological degeneration and profound deterioration of mental functioning
- Affects 4.5 million in US; 35.6 million worldwide
- By 2050: 14.3 million in US; 115.4 million worldwide
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Age onset for AD
- 65 and up and risk increases with age
- can develop before 60
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Biological Marker of AD
- Plaques (beta amyloid protein) that cluster among axon terminals (outside cell) above normal levels
- Interferes with neural communication
- Associated with cell death
- Beta amyloid protein is part of a larger molecule (amyloid precursor protein - APP) that is present in the cell membrane, but enzymes break up APP to make beta-amyloid protein
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Ī² secretase
- enzyme that cuts and determines how long the beta-amyloid protein is
- Either 40 (short) or 42 (long) amino acids
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In normal brains, _________ of beta-amyloid proteins are the shorts form
90-95%
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In AD brains, the long form of beta-amyloid rises to as much as _____
40%
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Pittsburgh Compoung B (PIB) PET scan
recognizes beta amyloid protein
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Neurofibrillary tangles
- Accumulation of neurofribrillary tangles (Tau protein)
- Tau protein is part of the microtubule system in axons
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Affected area of the brain in AD
- Hippocampus
- Entorhinal cortex
- Neocortex
- Locus coeruleus
- Raphe neuclei
- Shrinkage of the brain
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Basal Forebrain
cells that synthesize acetylcholine
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What happens to acetylcholine in AD?
- Beta-amyloid protein binds to receptor on Acetylcholine neurons and initiates cell death
- Cell death correlated with cognitive impairment
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Risk factors of AD
- Traumatic Brain Injury
- Diabetes
- Stroke
- Heart disease
- women's health
- loss of ovarian hormones (estrogen and progesterone) during menopause is thought to be related)
- smoking
- heavy smokingĀ
- nicotine binds to acetylcholine receptors
- mitochondrial dysfunction
- damage releases free radicals
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Early onset AD
associated with a mutation on chromosomes 21, 14, or 1
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Late onset AD
associated with gene on chromosome 19
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Treatment for AD
- Acetylcholinesterase inhibitors
- Donepezil (aricept)
- Rivastigmine (exelon)
- Galantamine (razadyne)
- Tacrine (cognex)
- NMDA antagonist used (glutamate binds to NMDA receptor)
- Memantine (Namenda)
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Dimebon
Remove accumulation of beta-amyloid peptide from the brain by taking advantage of the immune system
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Bapineuzumbab
Inhibits cell death by inhibiting NMDA receptors and enhancing mitochontrial function and enhances acetylcholine by inhibiting cholinesterase
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