Neurodegenerative diseases? Flashcards
What is neurodegeneration?
Progressive loss of neurones beyond that of normal ageing.
Neurones are not replaced…
Most ND - AGE is biggest risk factor.
Can include: vascular/circulatory (stroke), trauma, cancer.
What is venous infarction?
Usually results from venous sinus thrombosis.
risk factors - hyperviscosity and increased coagulation, very haemorrhagic!!
What is the penumbra and topography of ischaemic brain injury?
What is meningitis?
Infection of the meninges - membranes on outside of brain that covers the brain and spinal cord.
Can be bacterial, fungal or viral infection - Tuberculous mengitis is most dangerous infection
What is Polio?]
What was neuroscience findings of polio?
Poliomyelitus - caused by RNA poliovirus.
Only 3% of cases does the RNA poliovirus infect the CNS - in 1% of cases is there focal loss of spinal cord motor neurones.
Mapping of motor neurone foci in spinal cord to the innvevated muscle - demonstrated medio-lateral and anteior/posterior map.
- study spinal motor neurone loss and compare to resultant loss of muscle control.
Why are ND so special?
Cause is often unknown - Alzheimer’s understood of pathogenesis - but not what triggers the onset.
NO CURES - neostigmine can address some symptoms but doesn’t delay onset or halt progression of disease.
Progressive.
Often age dependent.
Inherited disorders are usually dominant alleles.
Summary of Alzheimer’s, Prion disease, Parkinson’s?
Alzheimer’s - most common form of dementia:
Deposition of beta-amyloid plaques and hyperphosphorylation of tau leads to tangles.
-Gross cerebral atrophy.
Prion disease - transmissable protein, with rapid progression and changes to vacuoles…
Parkinson’s disease - Hypokinetic - loss of dopaminergic neurones in SN with Lewy Bodies - alpha synuclein.
What are the amyloidogenic diseases?
Alzheimer’s, Parkinson’s and Prion diseases.
Prion - amyloidogenic prion protein forms extracellular aggregates and leads to changes in vacuoles.
Parkinson’s - alpha synuclein aggregates to form intracellular Lewy bodies.
Alzheimer’s - aggregation of extracellular beta-amyloid plaques and hyperphosphorylation of tau, leads to plaques and tangles.
What is the cause of Alzheimer’s?
Amyloid cascade:
Abnormal cleavage of amyloid precursor protein by beta-secretase forming and further cleavage by gamma-secretase leads to insoluble beta-amyloid.
Mutations in Presenilin genes:
Presenilins are domains of TM proteins that regulate cleavage of B-amyloid precursor protein - mutations in Presenilin genes increase production of Beta-amyloid peptide and contribute to 20-50% of early-onset cases of Alzheimer’s
Tangles - Tau is hyperphosphorylated in abnormal sites when non-MT associated.
Hyperphosphorylated Tau deposition seems to come first - but may play role in beta-amyloid deposition.
= HIGHLY DISPUTED.
Metal hypothesis - Cu, Zinc and iron are all concentrated in amyloid plaques in Alzheimer’s disease.
Beta amyloid involved in binding copper - metal accumulation may play role in causing disease.
What is Parkinson’s disease?
NOT a DEMENTIA!!!
2nd most common ND disease.
Hypokinetic disorder can symptomise as resting tremour, difficulty initiatiing motor movement, due to loss of dopaminergic neurones in zona compacta of Substantia Nigra - SNc.
SN is essential component of Basal Ganglia - modifying motor behaviour through projections to cortex via the thalamus.
Balancing Direct and Indirect pathways through innervation of Caudate/ putamen - regulation of fine motor control.
Mutant alpha-synuclein aggregates form intracellular Lewy bodies - causing oxidative stress and mitochondrial dysfunction - leading to cell death.
Mutant Parkin - Parkin usually proteolytically leaves alpha synuclein - mutant parkin fails to cleave alpha synuclein, allowing it to aggregate in Lewy Bodies.
Leads to reduced cortico-spinal output.
What are Prion Diseases?
V. rare.
Human and Animal diseases - Kuru - cannibalism of people infected with CJD, Mad cow disease (BSE)..
Protein-only hypothesis:
Abnormally folded PRION protein is highly transmisssable.
Long incubation period - 10-40 years.
Deposition of large amounts of abnormal prion proteins which are neurotoxic.
Once symptomatic - short death.
Leads to rapid neuronaal loss, Gliosis and Vacuolar
