Neurological Diseases alzheimers

Question 1

what is dementia defined as
some exapmles

Answer 1

progressive deterioration of cognitive function
short term memory loss
long term memory loss

Question 2

how is AD different from dementia

Answer 2

rapid cognitive decline

Question 3

what are the clinical symptoms of AD

Answer 3

memory loss
abnormal behavouir

Question 4

what is the main risk factor for AD

Answer 4

age
incidence doubles every 5 years

Question 5

how many people have dementia in the uk and how much does this cost the healthcare system

Answer 5

over 500 thousand
costs 35 billion a year

Question 6

what are the pathological hallmarks of AD

Answer 6

amyloid plaques
intracellular neurofibrillary tangle
non fungible tokes

Question 7

between the two hallmarks of AD
which is intracellular and which is extracellular

Answer 7

amyloid plaques are extracellular and nfts are intracellular

Question 8

what are some of the theories behind AD pathogenesis

Answer 8

amyloid cascade hypothesis
tau and tangle hypothesis
mitochondrial dysfunction and ox stress hypothesis
cholinergic hypothesis

Question 9

what is the app in AD

Answer 9

large extracellular protein produced in large quantities in neurons
undergoes post translational processing

Question 10

what are the three secretases involved in the cleavage of app in AD

Answer 10

alpha beta and gamma

Question 11

what are the two product catagories of amyloid secretases

Answer 11

pathogenic and non pathogenic

Question 12

which two secretases cleave app in non AD

Answer 12

alpha and gamma

Question 13

what are the products formed by alpha secretase in the non amyloid in AD

Answer 13

alpha cleaves app to create soluble appa(released)
membrane associated c terminal fragment actf(c83)

Question 14

what are the products formed by gamma secretase in non amyloid

Answer 14

gamma cleaves acft to make p3
and aicd

Question 15

what are the products formed in the amyloid process in AD

Answer 15

sappb
c terminal fragment beta(c99)

gamma secretase then cleaves beta cft to form beta amyloid peptide and aicd

Question 16

why do beta amyloid peptides cause AD

Answer 16

increased formation and defectiv clearance of beta amyloid causes plaques
beta amyloid is neurotoxic

Question 17

what causes familal AD

Answer 17

mutations in app or secretases cause AD

Question 18

what are nfts formed from

Answer 18

intracellular aggregates of tau protein

Question 19

what is the tau protein in AD

Answer 19

a microtubule associated protein
promotes microtubule assembly
and maintains stability

Question 20

how is the binding of tau to microtubules mediated in AD

Answer 20

phosphorylation state

Question 21

what does hyperphosphorylation do to tau in AD

Answer 21

decreases its binding to microtubules
decreased binding leads to tau aggregation
causes confirmational changes and misfolds in protein structure

Question 22

what is cholinergic hypothesis for ad

Answer 22

the reduction in acetylcholine release leads to AD

Question 23

in AD why is there a reduction of ach synthesis

Answer 23

deficit in enzyme
ChAT choline acetyl transferase

reduction of ach in neuron depolarisation

reduction of ach reuptake

loss of cholinergic neurones

Question 24

what is the reasoning behind mitochondrial dysfunction theory of ad

Answer 24

dysfunction increases with age
which leads to compromised atp production and oxidative stress
contributes to neuronal death

Question 25

what are the two main drug classes used to treat ad

Answer 25

cholinesterase inhibitors
nmda receptor antagonist(MDMA)
cholinomimetic therapy
acetylcholinesterase inhibitors

Question 26

what to acetylcholinesterases inhibitors do

Answer 26

prevent breakdown of ACH
increase concentration
increase communication

Question 27

what neurotransmitter is released in later stages of AD

Answer 27

glutamate

Question 28

what can glutamate do in ad and which drug class counters this

Answer 28

can cause further damage
NMDA blocks glutamate