Alzheimer's disease

Question 1

what are the 3 characteristics of Alzheimers neuropathology

Answer 1

cerebral atrophy
beta-amyloid plaque
neurofibrillary tangles (tau)

Question 2

what happens to the ventricles in severe AD

Answer 2

enlarged due to filling with cerebral spinal fluid

Question 3

are beta amyloid plaques intra or extracellular

Answer 3

extracellular

Question 4

are tau tangles intra or extracellular

Answer 4

intracellular

Question 5

where does degeneration begin in AD

Answer 5

nucleus basalis

Question 6

describe the spread of AD

Answer 6

nucleus basalis - projection areas (hippocampus and amygdala) then throughout the neocortex

Question 7

what are some symptoms of AD

Answer 7

• inability to complete daily tasks
• memory loss
• loss of cognitive and motor function

Question 8

name the enzyme that converts choline and actetyl coenzyme A into Ach

Answer 8

choline acetyltransferase

Question 9

what two receptors does Ach work on

Answer 9

muscarinic and nicotinic receptors

Question 10

what two enzymes catalyses Ach

Answer 10

acetylcholinesterase
butylcholinesterase

Question 11

where does butylcholinesterase work?

Answer 11

liver, plasma, skin, GIT

Question 12

what does acetylcholine get broken down into

Answer 12

choline and acetate

Question 13

name two regions of Ach neurons and their role

Answer 13

striatum - motor movement
lateral tegmental area - REM sleep

Question 14

what is the principal site of cholinergic cell bodies

Answer 14

nucleus basalis

Question 15

who first identified Ach was depleted in AD

Answer 15

Davies and Maloney

Question 16

what did Davies and Maloney propose - what does this mean

Answer 16

the unitary transmitter hypothesis - the idea that AD results from a depletion of Ach

Question 17

give two pieces of evidence in favour of the cholinergic hypothesis

Answer 17

cortical activity of choline acetyltransferase is reduced

massive loss of cholinergic neurons in the nucleus basalts of meynert and other basal forebrain areas.

Question 18

what is the acetylcholine precursor approach to treatment

Answer 18

administrating supplements of choline to boost production of Ach - not effective as 99% of choline enters other pathways

Question 19

how do acetylcholinesterase inhibitors work

Answer 19

prevent the destruction of Ach = more in the synaptic cleft

Question 20

how does memantine work

Answer 20

non-competitive antagonist of NMDA receptors

Question 21

name a Ach inhibitor

Answer 21

donepezil

Question 22

what are the side effects of donepezil use

Answer 22

nausea
vomitting

Question 23

what are the side effects of memantine

Answer 23

dizziness
headaches

Question 24

what is the ideal dosage for Achei drugs

Answer 24

patients start at low dose before gradually increasing based on the patients tolerance

as side effects are found at high dosages

Question 25

is donepezil selective or non-selective - what does this mean

Answer 25

selective - only inhibits cholinergic neurons (not peripheral neurons)

Question 26

name a non-selective acetylcholinesterase inhibitor

Answer 26

tacrine - it is not specific to the brain

Question 27

what is glutamate associated with

Answer 27

learning and memory

Question 28

describe the glutamate pathways

Answer 28

descending pathway from the prefrontal cortex to the brainstem

Question 29

how is the glutamatergic system affected in AD

Answer 29

reuptake is altered and a decrease in glutamine synthetase activity is seen

Question 30

what does glutamine synthetase do?

Answer 30

protects neurones from excitotoxicity

Question 31

what happens in excitotoxcicity

Answer 31

steady supply of glutamate = excessive calcium influx which activates enzymes = lots of free radicals

this can damage the structure of the neurons resulting in cell death