Demyelination and Dementia Pathology Flashcards
What differenciates demyelinating disorders from neurological disorders which damage myelin and oligodendrocytes eg trauma?
there is preferential damage to myelin sheath
What can the diganosis of MS be supported by in terms of investigations?
slowed conduction in conduction studies and IgG oligoclonal bands in CSF
What part of the brain does MS principally affect?
white matter- this is where myelinated axons are
What are MS plaques?
well circumcribed and well demarcated irrregular shaped areas which have a glassly appearnace
Where are MS most commonly seen?
aroun small vessels -CNII; periventricular white matter; corpus callosum; brainstem and spinal cord
What is seen histologically in active plaques?
perivascular inflammatory cells; microglia (eating myelin) and ongiong demyelination
what is seen histologically in inactive plaques?
gliosis; little remaing myelinated axons and few oligodendroctes
What is dementia?
an acquired nad persistent generalised disturbance of higher mental functions in an otherwise fully alert person
How are neurodegenerative diseases characterised?
progressive loss of neurons typically affecting functionally related neuronal groups
What are the primary dementias?
alzhemiers; Lewy body; Pick’s (front-temporal); Huntingtons
What is seen macroscopically with Alzhemier’s?
cortical atrophy; widening of sulci and narrowing of gyri; hydocephalus ex vacuo
What areas of the brain are spared in alzhemiers?
occipital lobe; brainstem and cerebelilum
What is seen microscopically with alzhemiers?
extensive neuronal loss with astrocyte proliferation; neurofibrillary tangles; neuritic plaques; amyloid angiopathy
What are neurofibrillary tangles?
budnles of insoluble microtubules associated with tau protein in the cytoplasm of neurons
What are neuritic plaques?
focal, spherical collections of dilated , tortuous, neuritic process of neurones that surround a central smyloid core, often surrounded by peripheral reactive strocytes and microglia
What other name are neuritic plaques known by?
Abeta amyloid plaques;
Where are neurofibrillary tangles most commonly found?
hippocampus and temporal lobe
How is amyloid A-beta produced?
cleavage of amyloid precursor protein
What chromosome is amyloid precursor protein found on?
21
What is the commonest familial cause of alzhemiers and how does it work?
apolipoprotein E e4 allele which dysregulates APP
What chromosome is presenilin 1 found on?
chromosome 14
What chromosome is presenilin 2?
chromosome 1
What does abnormal production of A-beta amyloid result in?
A-beta oligomerisation which form amyloid fibrils and then plaques
What do neuritic plaques lead to?
astrocyte and microgial activation–excitotoxicity
What are the products of A-beta protein oligomerisation?
amyloid fibrils and A-beta oligomers
What is the most toxic lesion that is produced from oligomerisation of A-beta protein?
A-beta oligomers
What are the actions of A-beta oligomers?
enter synaptic space and cause excitotoxicity; tau hyperphosphrylation and mislocalisation- which also contributes to excitotoxicity
What is amyloid angiopathy?
A-beta builds up in the wall of arterioles which stiffens and thickens the vessel walls and compromises the BBB
What are the clinical differences between Alzhemiers and Lew body dementia?
Lewy body dementia has fluctuating cognitive dysfunction; frequent visual hallucinations and memory is affected later; has motor features of Parkinson’s
What is seen macroscopically with Lew body dementia?
degeneration of the substancia nigra
What is seen microscopically with Lew-body dementia?
loss of prigmented neurons; reactive gliosis and microglial accumulation with remaining neurones having Lewy bodies
What is a Lewy body?
discrete eosinophilic cytoplasmic inclusion consisting of a dense core, surrounded by fibrils of alpha-synuclein
How many CAG repeats are needed for Huntington’s disease to occur?
> 35 repeats
What is seen macroscopically with Huntington’s disease?
atrophy of caudate nucleus>putamen>globus pallidus with hydrocephalus ex vacuo; later cortical atrophy
What does atrophy of the caudate nucleus lead to?
loss of inhibitory regulation of motor activity
What does later cortical atrophy correspond to?
onset of dementia
What are the symptoms of Pick’s disease?
personality and behavioural change; speech and comm problems; changes in eating habits and reduced attention span
When is the typical onset of Pick’s disease?
between 50 and 60 years
Why is there personality changes in Pick’s disease?
frontal lobe atrophy
Why is there language issues with Pick’s disease?
temporal lobe atrophy
What is seen macroscopically with Pick’s disease?
extreme strophy of the frontal and temporal lobes
What are the histological hallmakrs of Pick’s disease?
Pick’s cells (swollen neurons) and Pick’s bodies ( intracytoplasmic filamenouts inclusions)
What type of protein is found in Pick bodies?
protein Tau
What is multi-infarct dementia?
deterioration of mental functioning due to cumulative damage to the brain through hypoxia as a reult of multiple blood clots within the blodd vessels supplying the brain
Is vascular dementia more common in males or females?
men
What is the defining clinical feature of vascular dementia?
patients are aware of their mental decifits which provokes depression and anxiety
What are hte differenes between Alzhemiers and vascular dementia?
vascular dementia has abrupt onset and a stepwise progression; patient will have a hx of HT or stroke which will be seen on CT or MRI
