Conference: Alzheimer's disease Flashcards
What genetic determinants contribute to the early on-set of AD?
Chromosome 21 - amyloid precursor protein
Chromosome 4 - Presinilin 1
Chromosome 1 - Presinilin 2
Genetic determinants that contribute to late on-set of AD?
Apo-E (epsilon 1,2,4)
note: Apo-E epsilon 4 is the most influential
What part of the brain is the most affected by shrinkage?
hippocampus (plays a major role in formation of new memories
As the cortex shrivels up, the areas damaged are
areas responsible for thinking, planning and remembering
what structural changes does the ventricles undergo?
They grow larger
clumps of protein that interfere with cell-to-cell communication in AD
beta-amyloid
Thread of ____ twist into abnormal tangles that lead to failure of transport system
tau protein
The proteases that cleave ____ malfunction and generate by-product “beta-amyloid”
APP
what does APP in the brain form?
amyloid plaques (recall: amyloid cascade pathway)
B-amyloid change the ______ events within the cell to change cell behavior
signal transduction
what type of kinase is involved in taking over functions within the brain cells and assist in progression of AD
Glycogen Synthase Kinase - 3 (GSK-3)
tau becomes inactive -> cytoskeleton becomes weak -> fibers twist and tangle -> damaging the cell -> brain cell death
what is formed?
neurofibrillary tangles
____ -> cleaves APP -> no formation of B-amyloid
Alpha secretase
What do you call the pathway with Alpha secretase as the initiator?
Non-amyloidogenic pathway
What secretase/s is involved in the amyloidogenic pathway?
Beta secretase
Gamma secretase
enzyme involved in the formation of neurofibrillary tangles?
kinase
What is/are the effects of amyloid plaques on the neurons?
Increases calcium concentration
alters tau protein kinase activity
neurofibrillary tangles _______ the microtubules and lead to impaired synpatic transmission
destabalizes
proteins misfold and undergo confirmational change -> oligomeric/fibril seeds are produced -> protofilaments
-> mature fibrils -> aggregate to form plaques
Fibrin formation model
proteins misfold and undergo confirmational change -> oligomeric/fibril seeds are produced -> _________
-> mature fibrils -> aggregate to form plaques
protofilaments
Decreased hormon levels in persons with AD
somatostatin & serotonin
This hormone increases cerebral blood flow, prevents neuronal atrophy and reverses nerve damage
estrogen
provides endogenous anti-inflammatory agent around glial cells and blood vessels in NEOCORTEX and HIPPOCAMPUS
norepinephrine
True about acetylcholine in AD patients
severe disturbances in cholinergic system
Inhibition of ACAT =
reduces beta-amyloid
function of ABCA1
Regulator of cholesterol efflux
free Apo-E results to
PROMOTOES Beta-amyloid aggregation
Apo-E containing HDL
INHIBIT aggregation of Beta-amyloid
What interferon stimulates inflammatory response?
type 1 INF
astrocytes are high in persons with AD and when activated can
produce prostaglandin/arachidonic acid -> mediate inflammation
what mineral inhibits toxicity of amyloid-beta?
ZINC
the mineral ______ when elevated increases the risk of AD
homocysteine
