PBD 4 Alzheimers
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Who was the first alzheimers patient?
August D, 51 years old
T/F alzheimers is considered a common form of dementia.
False, Rare (1890s-1980s)
What is the most commmon neuro degenerative disease?
Who is more likely to get alzheimers (gender wise)
Florida has _#_ of dementia patients as of 2010
Sporadic AD represents what percent of cases. When is its onset age normally?
T/F familial AD is the most common case.
False, 10%, age of onset is before 65 and is caused by APP, PS1, and PS2 genes.
Three clinical stages of AD
- Mild, moderate, and severe.
- Daily activities not interfered
- Daily activities significantly affected
- Require total care
Early stage AD shows a degeneration of _____ neurons. This results in what?
- short term memory loss
Mid stage AD shows degeneration of ____ lobe and affects what?
- Frontal lobe
- affects judgement, safety awareness, planning and other complex thinking
late stage AD neurogeneration spreads ______.
Clinical tests to diagnose AD are
- Mini mental state exam
- CT, MRI, PET
- and tests that can affect memory/cognition
New clinical diagnosis for AD
Imaging for amyloid plagques and tangles in brain
T/F definitive diagnosis for AD can be done while someone is conscious.
False, POST MORTEM!
Cortical atrophy, ventricular dilation, amyloid plaques, tangles
AD brains have _____ gyrus and a ____ sulcus. They also have a dilated _____.
- Narrowed, widened
Amyloid plaques are ___-cellular whereas neurofibrillary tangles are ____-cellular
The core of amyloid plaques is made up of
beta Amyloid peptides
other components of amyloid plaques include
- B-amyloid proteins
- Apolipoprotein E
- protease inhibitors
- complement proteins
- Metal irons
APP stands for __ ___ ___. What are its 3 major variants? Where is the gene located?
- Amyloid precurson protein
- APP695, 751, and 770
- Chromosome 21
Functions of APP
- Cell-cell and cell-matrix interaction
- Cell growth
- synaptic plasticity
- cell surfact receptor
T/F sAPP is soluble and does not form aggregates.
alpha secretase cleavage causes formation of sAPP alpha into the ______ space
sAPPa regulates ____ levels and stimulates _____ _____.
- Signal transduction
Intracellular domain of sAPPa acts as adaptor protein for _-protein.
gamma secretase occurs ____ the membrane
AB 1-40 and 1-42 form ____ ____.
T/F AB 1-42 is more soluble than AB 1-40
T/F amyloid fibrils act as centers for deposition by other proteins.
AB peptides activate protein phosphorylation through this protein
T/F AB peptides are toxic to neurons
True, direct effect
T/F release of A-beta peptides are abnormal physiological events
mutations cause an (increase/decrease) of AB (1-40/42)
Less sufficient alpha secretase causes an (increase/decrease) of AB (1-40/42)
KNOW SLIDE 42!
slide 42, or what?
Presenilins 1 and 2 are membane proteins with ____ trans-membrane domains
Familial mutations is PS1 and PS2 increase gamme secretase activity leading to
increased AB generation
PS1 mutations are responsible for _%_ of early onset AD
PS2 mutations make up for _%_ of early onset AD
APP with downs syndrome has an (increased/decreased) APP expression which creates (more/less) AB1-40/42 and responsible for ____ formation at age 12.
Neurofibrillary tangles have microtubules with a diameter of __nm-______nm
Microtubule associated proteins include
Tau is found on chromosome __, it contains _ isoforms. It is important in proper neuronal axonal transport.
Increased phosphorylation of Tau and ubiquitylation causes formation of
PHF stands for ___ ___ ____ formed by detached ____ molecules.
- Paired helical filaments
GSK-3B and Cylin dependent kinase 5 are causes of _____ ____.
T/F E4/E4 has the lowest risk for AD
Apolipoprotein E4 is located on what chromosome?
Most abundant apolipoprotein is
T/F ApoE4 does affect APP expression
False, it does NOT
ApoE4 enhances _______ of AB and decreases _____ of AB.
Drugs for AD are mainly
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