BMC L8 Flashcards
(39 cards)
PaNuclues
Cluster of neurones in brain
Ganglion
Cluster of neurones in spinal cord
Plexus
Many ganglion connected together
Name 6 neurogenative diseases
SHAPE CJD
Schizophrenia
Huntingsdon Disease
Alzheimers disease
Parkinson’s disease
Epilepsy
CJD
What is AD?
Alzheimer’s disease:
Slow, progressive, neurodegenerative disorder
Most common form of dementia
State 2 causes of AD
- Intracellular accumulation of tau proteins as NFTs, neurofibrillary tangibles
- Extracellular amyloid plaques
State the symptoms of AD
- Short term memory loss, easily missed, not diagnosed
- Long term memory loss, confusion, loss of language, irritability, agression
- Loss of bodily function
- Death, usually 7 years after diagnosis
AD diagram - brain of patient
Pay attention to:
Cortex (sulci) - shrinks
Hippocampus - shrinks - memory, spatial navigation, consolidation of info
Ventricles - expand
White matter - shrinks
In general, brain shrunken
Perirhinal cortex shrinks - memory, navigation
Entorhinal cortex shrinks - Object perception, memory
How do we distinguish Familial / Genetic AD
- Early onset <65
- Autosomal dominant
- Loss of bodily function, loss of memory, progressive aphasia
What does the cholinergic hypothesis of AD postulate?
Oldest theory, postulates loss of ACh as cause
Basis of current drug therapies
Drugs which combat ACh loss not effective
Explain the Amyloid hypothesis of AD
“Extracellular accumulation of beta amyloid plaques/deposits”
- Proteolysis of APP (amyloid precursor protein, unknown function, found in synapses) leads to formation of beta amyloid deposits
- Beta amyloid deposits accumulate as extra cellular plaques
- This is neurotoxic - toxic to surrounding neurones
Why are Downsyndrome patients likely to develop AD by age of 40?
Amyloid hypothesis of AD.
APP gene - chromosome 21
Downsyndrome patient - trisomy chromosome 21
How is APOE4 a risk factor of AD?
Apolipoprotein
Risk factor
Isoform of APP
Breaks down beta amyloid plaques
What is the role of tau protein?
Tau protein binds to microtubules and stabilises them and helps them assemble
The tau protein is phosphorylated by kinase. It then forms Tau-P. Tau-P is what binds to the microtubules and stabilises them
Tau-p is dephosphorylised by phosphatase, forming tau, so it then dissociates from microtubules causing them to diassemble
Explain the tau hypothesis
Tauopathis, abnormal phosphorylation - Hyperphosphorylation - tau phosphorylates into helical paired filaments forming NFTs
NFTs (neurofibrillary tangles) are toxic to surrounding neurones
NFTs formed in the cell early (intracellular)
NFTs formed out cell later (extracellular)
Why may the tau hypothesis be unreliable?
Because the evidence contradicts whether tau-p binds or dissociates from microtubules
How can we detect AD?
PET scan of brain
Iluminates Tau Protein and Amyloid Plaques
Different pattern for Tau protein
Tau protein - usually found in hippocampus
Explain the noradrenergic hypothesis of AD
Loss of noradrenergic neurones in locus coerulus - OCCURS IN BOTH, AD, PD
Leads to symptoms of AD
Locus coeuruleus innervates hippocampus, spinal cord, cerebellum
How can AD lead to psychiatric depression and psychosis?
Noradrenergic hypothesis:
Loss of noradrenergic neurones, therefore, loss of noradrenaline.
What is Parkinson’s Disease?
Slow, progressive, neurodegenerative disease
- Loss of cells in substania nigra - diminishing of substantia nigra
- Less dopamine produced
- Increased output from basal nuclei
- Reduced activity of thalamus
- Reduced output of cerebral cortex
- Hypokinetic disorder
What is the substantia nigra? Describe its location and function.
Linked to basal ganglia via midbrain
Crescent shaped mass of cells
Sends neurones to tissues on both side of brain
Therefore, helps control coordination and movement
Describe the structure and location of the basal ganglia.
Basal ganglia located in midbrain.
Consists of
-Striatum - Caudate nucleus + putamen
-Corpus striatum - Striatum + globus pallidus
-Subthalmic nucleus
-Substantia nigra - dopaminergic region
Explain the Lewy Body theory of PD
Lewy bodies are round inclusions of polymerised alpha synuclein proteins found in the cytoplasms of neurones in the substantia nigra
alpha synuclein found at pre-synaptic terminals, function unknown, involved in synaptic vesicles
leads to rare genetically inherited form of PD
Explain the Parkin theory of PD
Parkin - involved in degradation of proteins
Mutation to parkin leads to a more common genetically inherited form of PD
“Juvinile PD”
Autosomal recessive
Early onset (<45)
