Exam 4: AD

Monday, April 23, 2012 8:32 AM

1. 1/8 persons over the age of 65 have AD. 2. To get the definite conclusion on whether someone has AD or not, you have to wait for that person to die and get an autopsy on their brain because other types of dementia exhibit AD like symptoms but it might not be AD. 3. Alois Alzeihmer was the first person who characterized this set of symptoms, characterized a 51 yr old woman w/ declarative and spatial memory disorders, disorientation in time and altered effect. Early onset. Genetic component. a. Neurofibrillary plaque and tangles in cortex (hallmarks of AD) i. Generally start out in areas important for learning and memory . Start out with hippocampal and medial temporal area. 4. Brain changes a. Extensive cell loss and reduction in synapses in the hippocampus b. Dystrophic neurites c. Abnormal ararngement of neuronal cytoskeleton (forming tangles in the brain) d. Functional disconnection of cortical and hippocampal circuitry. e. Acetylcholinergic neurons in basal forebrain are acmong the first cells to be affected by AD. i. Aricept: acetylcholinesterase inhibitor 1) Helps the brain to retain acetylcholine by not breaking it down so readily 2) Overall brain volume shrinks because of cell loss 5. Tau protein--responsible for tangles a. Makes up part of the microtubules that keep the neurons somewhat structured and organized. Microtubules important for transporting vesicles back and forth and structural component. When the brain starts to die, the tau protein that are part of microtubules become loose and find each other and make tangles. Clumps of tau protein that are not being cleared. Deposits of tangles all over the brain. b. Plaque: made of beta amyloid protein. i. Beta amyloid protein arises from BPP, beta amyloud precursor protein. ii. Two different assembly states. iii. Aggregated form (long form) non aggregated (short form). When beta amyloid is formed, it gets cleaved at the cell level, does its function (synaptic transmission), and you clear it out of your system after job is done. People who have AD, something goes wrong in this process and B-amyloid cannot be cleared out, so it accumulates (esp. long form) and you end up with beta amyloid plaque. iv. Either too much is made and clearing out system doesn't work or normal amount is made and clearing out system doesn't work properly. v. When the axons, dendrites come in contact with beta amyloid, it starts killing them. 6. Beta amyloid hypothesis a. When plaques come in contact with cells, the cells become disease and die off. Triggers cell death in AD brain. b. Plaques are in beta amyloid which causes cell death, so plaques cause AD c. Family history of having AD: genetic abnormalities include at chromosome 21 (APP gene, precursor to beta amyloid) and presenilin gene (abnormal production of long form of bet amyloid) and ApOE (interferes with removal of long form of beta amyloid). d. Transgenic mice, mutate APP, show effects of ADD at brain level and behaviorally 7. Researchers, study, antibodies against B amyloid. a. With mice, it was night and day difference. b. Human subjects: People who had antibody didnt get better or worse, stayed at baseline, maintained whatever cognitive ability they had at the beginning of the trial. Second phase, people showed reaction and the study was stopped.
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people showed reaction and the study was stopped. c. Other hypothesis--watch video 8. Treatment a. Aricept (acetylcholinesterase inhibitor) 9. Seeing AD brains a. Pittsburg compound B, like a PET scan, drink something or inject something into brain and can look at particular activity in brain (glucose utilization, dopamine activity). Pittsburg compound B attaches itself to B amyloid. You can see whether the person has B amyloid accumulating. Healthy brain--shouldn't see much. b. Groups of nuns who didn't show AD, cognitive functions intact, after passed away, found that brains had beta amyloid plaque and tau tangles.

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