neurobiology of dementia Flashcards
outline the neuropathology of dementias micro/macroscopically
microscopically: intraneuronal inclusion bodies, extraneuronal changes (plaques)
macroscopically: generalized brain atrophy, region-specific atrophy depending on dementia disorder, and enlarged ventricles.
what are the main causes of dementias
misfolding of proteins, abnormal accumulation, neuroinflammatory environment, damaged neurons, cell death, proteins involved: amyloid, tau and synuclein
Outline tau abnormalities
found in Alzheimer’s disease and frontotemporal dementias.
Outline Tau protein
6 isoforms of Tau
normal protein, highly soluble, mainly found in brain, mainly present in axons.
function: modulate the stability of axonal microtubules and with transport.
normal Tau will become diseased Tau if there is problems with activated kinases causing
hyperphosphorylation.
Outline amyloid protein
The second protein that can misfold in alzheimers,
APP is a transmembrane glycoprotein which is broken down and eliminated in the brain. APP is split into to forms and the most common forms are AB40 and AB42, those that are pregenetically determined to develop dementia have AB42 present more which is more fibrillogenic and is thus associated with disease states and build up of these plaques can lead to neuronal damage.
Outline frontotemporal dementia
Due to tau Pathology, neurons swell taking on balooned appearance, FTD is present in frontal and anterior temporal lobes.
What are some synuclein abnormalities
parkinson disease, dementia with lewy bodies and fibrillary aggregates of alpha-synuclein protein
Outline dementia with lewy bodies
synuclein which is found in neurons and glial cells, have a function of lipid vesicle binding, dopamine uptake, inhibition of pD2 and protein kinase c etc,
can aggregate to form intracytoplasmic inclusions in neurons (lewy bodies)
What do lewy bodies contain
spherical shaped, contains: alpha synuclein, ubiquitin and associated enzymes.
What is vascular dementia
not a neurodegenerative disorder but is a vascular disorder which results from ischemia or hemorrhagic brain damage. most common mechanisms causing the disease is: single, strategically placed infarcts.
multiple cortical infarcts, subcortical small-vessel disease.
What are the diagnostic steps in diagnosing dementia
history, examination, bloods/ecg, neuropsychological, behavioural/activities of daily living and neuroimaging.
Outline some treatments
AD- symptomatic treatment, donepezil, rivastigmine, galantamine, memantine.
vascular dementia: treat risk factors: hypertension, diabetes, hyperlipidaemia, AF and carotid disease and anticoagulants.
