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58 Cards in this Set
- Front
- Back
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ALOIS ALZHEIMEr
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51 year old
MEMORY Impairment Where's home 100 year anniversary |
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Age and AD
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85+ years old 1/2 have AD
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AD risk factors
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prevalance doubles for every 10 years after 60
Higher risks if relative affected (genetic component) Common in women Head trauma high cholesterol= brain's equivalent to heart attack Lack of mental stimulation |
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Greatest population at risk for AD
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Women who are illiterate
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26 points out of 30 points for test
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day of the week
What was last year? Building? |
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What happens in the brain with AD
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ATROPHY
Lost of neurons, loss of functions |
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What region of the brain is affected with AD?
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Hippocampal atrophy
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There is associated brain dysfunction with AD
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Statement.
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There are plaques and tangles in the AD brain
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Post mortem
Histologically: Brown crud layers Ameloid plaques Neurons start to fall apart Neuralfibur EAU- towel filaments |
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Original thoughts on cause of AD
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Loss of cholinergic systme
Damage to acetylcholine neurons Entire brain is affected leading to loss of memory |
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What is the major drug used to treat AD?
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ACHE (acetylcholinesterase) inhibitor
ARICEPT |
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Aricept
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ACHE
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Not simply a cholinergic problem, rather
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There was still oxidative damage throughout most of brain
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Drugs such as AcHesterase
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doesn't cure, eliminate symptoms
Same as insectisides |
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Beta amyloid load
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correlated with cognitive impairment
The more beta amyloid the lower the score |
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Amyloid hypothesis:
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Bad actor in the play
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What is the central molecule in AD
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amyloid
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Amyloid
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found in all plaques
aggregates into beta-pleated structure AKA beta amyloid |
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aggregate beta amyloid induces
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dose-dependent toxicity
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Vaccine to beta amyloid
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Therapeutic in mice with AD symptoms
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Mice with increase beta- amyloid
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Cognitive deficits
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Down's syndrome and AD
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increase beta amyloid- induce similar AD brain profile
Chromosome 21 is the same chromosome that amyloid is made from Plaques and tangles are developed in DS patients |
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What initiates AD
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Gamma-secretase
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What is gamma secretase's function
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Cleaves amyloid Precursor Protein (APP) into Amyloid beta 40 or 42
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Ab 40 or 42
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AD starts when more Ab42 is produced
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Precursor protein stuck in membrane of neuron
Cleaved by beta secretase Free fragment flows off |
Gamma cuts it either at ab 40 or ab 42
40 is cleared away 42 increased prevalence |
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Glutamate (Stress)
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Amyloid appears to block glutamate reputake by glial cells
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Increase in glutamate causes what
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increase NMDA receptor activation
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NMDA affects what ion concentration
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Intracellular Calcium
More calcium More cell death |
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What do you use to treat moderate to serious patients
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NMDA blocker, MEMANTINE
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MEMANTINE
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NMDA blocker
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Neurons die via
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Apoptosis:
membrane blebs, shinks, chromtin condenses, nuclear fragments, DNA breakdown NECROSIS comparison??!??!?!? |
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What is BDNF
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Brain derived neurotrophic factor
Not adequate nourishment and there is a decreased probability of growth |
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Inducers of apoptosis corespond to AD conditions
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beta amyloid that destroys neurons
Oxidative damage BNDF deficient reduced brain metaboliz Lipids Abnormal calcium binding (calcium causes cell death) |
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DNA damage
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found in many AD brain neurons
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Timing of apoptotic mechanism versus AD timing
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degeneration is not over DAYS but YEARS
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AD upregulates bcl2
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bcl2 protects against cell death due to beta amyloid
bcl2 keeps them alive; stops them from dying even though they are being damaged in serious way |
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DNA repair enzymes are higher in AD brains
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help repair initial damage by apoptotic cell programmed deat
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How to prevent AD?
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mental and physical activity
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Learning enhances what associated with AD
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Brain derived neurotrophic factor expression in HIPPOCAMPUS
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Increase in physical activity
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Increase in hippocampal BNDF
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Mice kept mentally and physically active produce
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5x HIPPOCAMPAL neurons than when in SOLITARY CAGE
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High fat and sugar diet
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decrease brain hippocampal
So calorie restrict |
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Stress and AD
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Stress decreases brain derived neurotrophic factor
Injected with stress hormone Upregulate beta amyloid |
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Rats with low BDNF levels
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poor learners
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Cholesterol and STATINS
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increase the processing of amyloid precursor protein (APP) by gamma secretase
Processing leads to decrease beta-amyloid production |
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Antioxidants and AD
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Vitamin E
slows process of alzeimers |
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If you have rheumatoid arthritis, you don't get AD
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take high levels of non-steroidal anti-inflammatory drugs (NSAIDs: ibuprofin)
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Inflammatory proteins in AD
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increase
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Aspirin vs. NSAIDS
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don't have protective effects
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AD and COX effects
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Not related
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Prednisone (STEROIDAL- anti-inflammatory)
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doesn't work on AD
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Ibuprofin affects
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gamma secretase (cuts and choose ab 40 or 42) to decrease amount of ab42
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Women
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have higher rate of AD
ESTROGEN?!?!?!? |
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Menopausal women vs. same aged men
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Men still have estrogen
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Hormone replacement theory
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lower rate of cognitive decline
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Factors that decrease
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Bilingual
Cognitive/motor activity Omega 3 oil Curry Fruits or fruit juices (antioxidants) Increase - Stress |
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Stress
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increases beta amyloid
Within 7 days Beta amyloid ab40 and ab 42 Beta amyloid 42 increases Dna damage Apoptosis |
