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