PBL 5 Flashcards
what is a cholinesterase inhibitor
stops acetylcholinesterase enzyme from breaking down acetylcholine.
define dementia
it is a chronic progressive neurodegenerative condition that results in impairments in cognition to impair acitivies of daily living
name types of dementia
alzheimers
vascular dementia
frontal temporal
dementia with lewy bodies
what 3 things is there a progressive decline of in dementia
o Memory and Reasoning
o Communication Skills
o Inability to carry out daily activities.
what other conditions does dementia need to be distinguished from
o Normal Ageing: mild, benign memory loss.
o Delirium: acute and reversible disturbance of higher mental function, usually associated with
impaired conscious level and caused by infection, toxic, metabolic substances.
o Pseudodementia: cognitive effect of severe depressive illness.
Difficult to separate from dementia as depression is often secondary to dementia.
o Apathy: loss of motivation that lacks the emotional content of a depressive illness.
what are early clinical features of dementia
Short-term memory loss.
Disorientation in time.
Reduced judgement and planning ability.
what are the modifiable risk factors and the non modifiable risk factors of dementia
non modifiable
- age
- genetic
- family history
- Down syndrome
modifiable
- vascular
- cognitive inactivity
- environment
- depression
what 2 pathological things characterise dementia
Senile/Neuritic Plaques (extracellular deposits of beta-amyloid peptide) particularly in the parietal
lobe/hippocampus.
Intracellular Neurofibrillary Tangles: hyperpolarized tau protein.
what are other structural hallmarks to dementia
Synaptic and neural degeneration
Severe atrophy of cerebral cortex (widening of the sulci).
Enlargement of the ventricular system.
what part of the brain is at risk of degeneration
- medial temporal lobe including the hippocapal complex and entorhinal cortex
what part of the brain is well preserved in the brain
Well preserved areas of the brain: primary sensory/motor
areas, upper regions of prefrontal cortex.
what 3 genes are responsible for early onset dementia
APP chromsome 21
presilin 1 chromsome 14
presilin 2 chromosome 1
what is APP function
Involved in helping neuron growth and repair.
o Over time APP is broken down and recycled.
where is APP expressed
Transmembrane protein expressed in neurons, glial cells, endothelial smooth muscle.
what are the two ways in which APP is recycled
non-amyloidogenic pathway
amyloidgenic pathway - pathological
describe the non amyloidgenic pathway
In normal non-amyloidogenic pathway, alpha and gamma
secretases do not form amyloid-beta peptides but cleave
up the protein into soluble form which is recycled.
describe the amyloidgenic pathway
In diseased amyloidogenic pathway, the transmembrane protein is wrongly cleaved by beta
and gamma secretases which leads to formation of non-soluble amyloid-beta peptides.
These peptides aggregate to form senile plaques
what subunits is gamma secreted made out of
(!) The γ-secretase is made up of subunits. Of
note are PSEN1 and PSEN2 because mutations in
these can cause Alzheimer’s (PSEN1 being the
most common).
what do the plaques do to the nervous system
Can potentially get in-between the neurons which disrupts signalling.
Therefore, impairs various functions like memory. o Start an immune response which causes activation of microglia. o Can also cause amyloid angiopathy when around cerebral vessels
Weakens walls and increases
risk of haemorrhage.
what is the normal function of TAU
Neurons are held together by their cytoskeleton made up of microtubules.
o Ship nutrients and molecules along the cell.
o Located within the neuron.
Tau stabilises microtubules through coordinated binding through kinases/phosphates.
