Neurophysiology 3 Flashcards
What is the Pathology of Alzheimers?
Amyloid beta plaques- that are Intracellular (specifically the mitochondria) and Extracellular.
Neurofibrillary tangles - composed of protein called Tau found deep within the cell.
What are the top 2 types of dementia?
1) Alzheimer’s Disease
2) Vascular Dementia
Tell me the features of Early Onset Alzheimer’s?
pre-65y (1-5% of cases)
Mutations in genes encoding:
Amyloid precursor protein (APP) (large protein produced in the brain which is chopped up into smaller fragments by enzyme activity one of them being amyloid beta. )
Presenilin 1 (component of γ-secretase)
Presenilin 2 (component of γ-secretase)
Affects production of Amyloid-β (Aβ1-42)
Mutations of these affect production of amyloid beta
Tell me the features of Late Onset Alzheimers?
Unknown cause
Genetic cause?
E.g. apolipoprotein E (ApoE)
Produced by the astrocytes
Function of ApoE – transport cholesterol into neurones
Thought that ApoE binds AB – regulated aggregation leading to inflammation of the brain
ApoE 4 form = mutation in gene – less effective in regulating aggregation = risk factor
What is the Amyloid Hypothesis?
Amyloid precursor protein (APP) is processed to a smaller protein AB - which accumulates as plaques in the brain leading to AD.
Evidence:
- APP gene; chromosome 21
- Downs Syndrome (trisomy 21); extra chromosome, extra gene, produce more AAP
- Invariably exhibit AD characteristics by 40 year old.
How is the Amyloid Precursor Protein (APP) processed to a smaller protein AB?
APP embedded in the membrane.
APP cut by an alpha secretase and gamma secretase.
Releases fragments which we use in the brain which helps with function of the synapse and learning and memory.
What happens when APP cut by Alpha Secretase?
When the Alpha Secretase cuts - soluble APP is released (normal process which happens all the time in our brains)
What happens when APP cut by Beta-Secretase?
When APP is cut by B- Secretase, it leads to amyloid beta (42 version) which is very poor in terms of solubility and these start to clump together in the brain.
What happens when APP cut by Beta and Gamma Secretase?
When B secretase and y secretase cut and process the APP, they produce AB insoluble peptide 42 mer.
Another fragment also produced (N APP) which binds to Neurone death receptor 6 and can lead to death as a consequence.
What is the Tau Hypothesis?
Problem with Tau Hypothesis?
- Microtubules: scaffolding and transport system (nutrients, molecules)
- They are a transport system within the cell
- Microtubules act as motorways trafficking components around the cell
- Phosphorylation: adding a phosphate group to a protein
- Phosphorylation of tau stabilised microtubules
- Problem is, when tau is hyperphosphorylated, microtubules start to disintergrate leading to neurofibrillary tangles
- Unable to move compounds through the cells and they start to die.
What are the affected areas of the brain for AD? In Order?
1. Hippocampus • 1. New memory formation • Cf memory retrieval 2. Amygdala • Emotional recall
- Cortex
• Memories from longer ago are lost
What is an Ischemic Stroke?
Most common type of stroke.
Disrupting blood supply to the brain (could be due to various things).
Clot, and, Plaque.
Mostly due to lifestyle diet, exercise and statins.
What is treatment for Ischemic Stroke?
Treatment is extremely limited:
- Tissue plasminogen activator (Alteplase) -> thrombolytic effect.
What is a Haemorrhagic Stroke?
Treatment?
Bleeding into the brain.
Surgery - Craniotomy
- Remove clot
- Repair burst blood vessel
- Blood Pressure (ACE inhibitors, beta-blockers), lifestyle, exercise.
What happens during a stroke?
- Cells deprived of nutrients and O2
- Cell death and brain damage
- Two areas to stroke:
o Inner area: Umbra – so much damaged that tissue cannot be repaired
o Penumbra: around the core of the stroke there is potential for recovery
