Neurological Diseases alzheimers Flashcards
(28 cards)
what is dementia defined as
some exapmles
progressive deterioration of cognitive function
short term memory loss
long term memory loss
how is AD different from dementia
rapid cognitive decline
what are the clinical symptoms of AD
memory loss
abnormal behavouir
what is the main risk factor for AD
age
incidence doubles every 5 years
how many people have dementia in the uk and how much does this cost the healthcare system
over 500 thousand
costs 35 billion a year
what are the pathological hallmarks of AD
amyloid plaques
intracellular neurofibrillary tangle
non fungible tokes
between the two hallmarks of AD
which is intracellular and which is extracellular
amyloid plaques are extracellular and nfts are intracellular
what are some of the theories behind AD pathogenesis
amyloid cascade hypothesis
tau and tangle hypothesis
mitochondrial dysfunction and ox stress hypothesis
cholinergic hypothesis
what is the app in AD
large extracellular protein produced in large quantities in neurons
undergoes post translational processing
what are the three secretases involved in the cleavage of app in AD
alpha beta and gamma
what are the two product catagories of amyloid secretases
pathogenic and non pathogenic
which two secretases cleave app in non AD
alpha and gamma
what are the products formed by alpha secretase in the non amyloid in AD
alpha cleaves app to create soluble appa(released)
membrane associated c terminal fragment actf(c83)
what are the products formed by gamma secretase in non amyloid
gamma cleaves acft to make p3
and aicd
what are the products formed in the amyloid process in AD
sappb
c terminal fragment beta(c99)
gamma secretase then cleaves beta cft to form beta amyloid peptide and aicd
why do beta amyloid peptides cause AD
increased formation and defectiv clearance of beta amyloid causes plaques
beta amyloid is neurotoxic
what causes familal AD
mutations in app or secretases cause AD
what are nfts formed from
intracellular aggregates of tau protein
what is the tau protein in AD
a microtubule associated protein
promotes microtubule assembly
and maintains stability
how is the binding of tau to microtubules mediated in AD
phosphorylation state
what does hyperphosphorylation do to tau in AD
decreases its binding to microtubules
decreased binding leads to tau aggregation
causes confirmational changes and misfolds in protein structure
what is cholinergic hypothesis for ad
the reduction in acetylcholine release leads to AD
in AD why is there a reduction of ach synthesis
deficit in enzyme
ChAT choline acetyl transferase
reduction of ach in neuron depolarisation
reduction of ach reuptake
loss of cholinergic neurones
what is the reasoning behind mitochondrial dysfunction theory of ad
dysfunction increases with age
which leads to compromised atp production and oxidative stress
contributes to neuronal death
