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
