L21: Ageing Brain Flashcards
In a normal ageing brain what are the 4 broad types of changes that occur
Macroscopic changes
Cellular changes
Molecular changes
Clinical changes
What are the macroscopic changes that occur in a normal ageing brain
Ventricular enlargement
Cortical thinning
Decrease post morgen weight
Accumulation of more white matter
What are the cellular changes that occur in the normal ageing brain
Axonal loss
Mitochondrial changes
Less synapses per cell NOT number of cells
What are the molecular changes that occur in a normal ageing brain
Altered gene expression of key neurotransmitter
Disrupted calcium signalling
Epigenetics changes
What are the clinical changes that occur in a normal ageing brain
Cognitive decline
Decreased well being
Low mood
Increased risk of neurodegenerative disease
When the synapses change in which area is it most affected
Pre-frontal cortex Hippocampus Striatum Temporal lobes Cerebellum
What happens to the number of microglia with age
Increase
What are functions of microglia cells
- clear debris such as beta amyloid
- trigger repair by astrocyte stimulation stem cell recruitment to convert it to astrocytes
- release growth factors and neurotrophins
What are the 2 ways which microglia cells become activated
- inflammation which switches it to M1 to MHC2
- damage to astrocytes
What are the changes that occur at the synapse of neurotransmission
- mitochondria do not function well and produce less ATP so less neurotransmitters are exocytosed
- change in gene expression of transporters that get neurotransmitter into the synaptic space
- changes in number and affinity of post- synaptic receptors
- changes in calcium homeostasis that usually triggers AP so AP is affected
What happens to the level of dopamine
Decreases
What happens to the level of acetycholine
Decreases
Why does ach levels decrease
Reduction in the enzyme CAT that converts the ach precursor into ach
What happens to the levels of GABA
Decreases
Why does GABA levels decrease due to
Decrease in GAD enzyme that produces GABA
What are the types of memory in a normal brain and what are they associated with
Semantic memory: factual memory
Episodic memory: events
Working memory: thinking and saying something
Procedural memory- memory tasks e.g riding a bike
Does Alzheimer’s disease have treatment
No
What is the hypothesis that suggests pathology for Alzheimer’s disease
Amyloid hypothesis
What is the amyloid hypothesis about
Accumulation of beta amyloid which triggers inflammation reaction that leads to cell death
What is amyloid beta a derivative of
Amyloid precursor protein (APP)
What are the 2 types of intellectual failure
Mild cognitive impairment
Delirium
What is mild cognitive impairment
When people have a cognitive deficit but not dementia
It does not affect normal functioning
What is delirium
Occurs with age
What is dementia
A chronic syndrome that impairs cognition not just memory and affects everyday function
What are the causes of dementia
Alzheimer’s disease Vascular disease Lew body dementia Fonto-temporal dementia Posterior corticol atrophy
Describe the process that occurs in the amyloid hypothesis in Alzheimer’s
1) there is a missense mutation in APP, PS1, PS2 gene
2) this leads to increased production of amyloid beta and accumulation
3) as amyloid beta accumulated it joins together to from plaques
4) plaques affect the synapses and activate microglia and astrocytes (inflammatory cells)
5) inflammation coupled with plaques leads to changes in the synapses
6) this affects the enzymes kinase and phosphatase that lead to tangles
7) this leads to damage to neurones and neurotransmitters accompanied with cell death
8) tau also occurs intracellular
When can Alzheimer’s disease be inherited
If there is a missense mutation of the APP gene
When is Alzheimer’s disease sporadic
Due to age and failure of amyloid beta clearance mechanism
Therefore there is accumulation of amyloid beta in the brain
What is the difference between the number of cells in a normal ageing brain and Alzheimer’s
Normal ageing brain: same number of cells but smaller
Alzheimer’s disease: less number of cells due to cell death
