Dementia Flashcards
What differences between a dementia and a non dementia brain can be seen on a PET scan?
Neuronal loss
Hypometabolism
Loss of grey matter
Ligher
In which 3 areas of function is there a progressive decline in ability in dementia
- Decline in memory and reasoning
- Decline in communication skills
- Inability to carry out daily activities
What behavioural and psychological symptoms are seen in dementia
Agitation Aggression Wandering Shouting Repeated questioning Sleep disturbance Depression
4 non-modifiable risk factors for dementia
- Age
- Genetic predisposition
- Family history
- Downs syndrome
4 modifiable risk factor for dementia
- Vascular risk factor
- Cognitive inactivity
- Environment
- Depression
What 2 structures can be seen in the brain in dementia
Plaques
Tangles
What protein is present in senile plaques and cerebral vessels in alzheimers disease
Beta-amyloid peptide
What protein is present in neurofibrillary tangles
Hyperphosphorylated tau protein
Do cholinergic cells increase or decrease in number in AD
Decrease significantly
What % of AD cases are classified as early onset
<5%
Name the 3 genes identified to be involved in early onset AD
Amyloid precursor protein (APP) Presenilin 1 (PSEN1) Presenilin 2 (PSEN2)
What kind of protein is amyloid precursor protein
Single transmembrane protein
Where is APP expressed normally (4)
Neurones
Glial cells
Endothelial cells
SMC
What is APP cleaved to form
Amyloidogenic A-beta peptides
What are mutations in APP associated with
Familial forms of early onset Alzheimers
Cerebral amyloid angiopathy
What does A673T mutation do
Decreases a-beta production and it protective of AD
What does PSEN1 encode for
PSEN1 encoding presenilin-1
This is a subunit of gamma secretase
How much mutations have been reported in
a) PSEN1
b) PSEN2
c) APP
a) 189
b) 24
c) 29
What does PSEN2 encode for
Gamma sacretase- aspartyl protease responsible for A-beta generation
What enzymes cleave APP (transmembrane polypeptide)
alpha, beta and gamma secretase
Describe the APP processing pathway that is non-pathogenic
- Alpha and gamma secretase cleave APP
- Derives P3 and C83
- No AD
Describe APP processing pathway that is pathogenic
- Beta and gamma secretase and generates a beta amyloid peptide (39-43)
- This is a pathogenic peptide
What 2 explanations have been suggested to explain amyloid proteins involvement in AD
- Overproduction of amyloid and oligomers
- Inability to remove amyloid
What are the sequence of steps that result in familial forms of AD (10)
- Genetic missence mutations in APP, PS1, PS2
- Increased proteolysis and production of APP
- Progressive accumulation of a-beta in brain interstitial fluid
- Deposition of aggregated A-beta40/ a-beta42 as plaques
- Inflammatory response
- Progressive neuritic injury within amyloid plaques
- Disruption of neuronal metabolism and ionic homeostasis
- Altered kinase/ phosphatase activity– hyperphosphorylated tau
- Formation of hyperphosphorylated tau protein
- Widespread neuronal/ neuritic dysfunction and death in hippocampus and cerebral cortex
