WEEK 4 Flashcards
HOW DO cholinesterase inhibitors work
these increase brain acetylcholine levels by inhibiting CNS acetylcholinesterase . effective in Demetia with LB and parkinsons demetia but not FTD/vascular demetian. effective in mild/moderate AD
what is glutamate
an amino acid , the major excitatory neurotransmitter
characteristics of NMDA receptors
permeable to calcium ions
the ion channel is blocked by magnesium - voltage dependent blockade
long term potentiation - slow gated kinetics
Clinical features of Alzheimers disease
*failing memory- episodic mem affected
*cognitive decline
*psychiatric - personality changes
*neurological - primitive reflexes and postural abnormalities
impairment of organising planning and sequencing . there is visuospatial difficulties
pathological changes in the brain - preclinical AD
signs of AD first noticed in the entorhinal cortex, then the hippocampus . AD spreads through the rbain , the cerebral cortex begins to atrophy with more neuronal loss . affected regions begin to atrophy with associated neuronal loss . memory loss is the first sign .
mild AD
memory loss, confusion, trouble handling money , poor judgement , anxiety , mood changes
moderate AD
increased mem loss and confusion problems recognising people , difficulty with language and thoughts
wandering
repetitive statements
severe AD
- Severe cortical atrophy. Pathology throughout the neocortex.
- Patients are completely dependent requiring nursing home care.
- Weight loss, seizures, increased sleeping, loss of bladder and bowel control.
- Death usually occurs from pneumonia.
PATHOLOGY hall marks for AD
- Deposition of β-amyloid (Aβ) in amyloid plaques in the cortex
- Tau containing intracellular neurofibrillary tangles.
- These proteins aggregates damage synapses and ultimately lead to neuronal death.
- Amyloid may also be laid down in cerebral blood vessels, leading to amyloid angiopathy
WHAT is amyloid precursor protein
is a glycoprotein molecule that sits in the cytoplasm - essential component of neuronal membranes . it has 3 parts and thus can be cleaved off by the enzyme secretase , there are types of secretase - alpha beta gamma
possible mutations of APP
- Point mutations in the APP gene.
- Mutations in the presenilins 1 & 2 (affect gamma secretase)
- Polymorphism of the E4 allele of the apopliprotein E is associated with a 20x higher risk of developing AD
cleavage of APP releases what
beta-amyloid in the extracellular matrix , these then aggregate into plaques , which are harmful to neurons. beta amyloid may also be laid down in cerebral blood vessels leading to amyloid angiopathy
what is amyloid angiopathy
Aβ may also be laid down in cerebral blood vessels,
mutation of tau protein
- Within neurones, the transport system is organised in orderly parallel strands. biomolecules and cell parts move along these strands.
- However, when there is hyper-phosphorylation of the tau protein, it collapses into twisted strands called tangles. The strands can no longer stay straight and thus fall apart and disintegrate. Nutrients and other essential supplies can no longer move through the cells, which eventually die.
- The tau strands then aggregate into neurofibrillary strands
what is vascular demeNtia
Effectively a series of mini strokes , causing damage to the brain thus memory. patient often has a series of trasient ischaemic attacks to the brain.
demetia with lewy bodies pathophysiology
• The lewy bodies formed are aggregates of the protein α-synuclein. This is due to the protein misfolding into a β-pleated sheet structure. These then further aggregate into higher-order insoluble structures (fibrils), which are the building blocks for Lewy bodies.
