Alzheimers Flashcards
Main risk factor for alzheimers
Age
Clinical symptoms of alzheimers
Memory loss
Poor judgement
Personality changes
Confusion
Theory behind pathophysiology of alzheimers
Amyloid hypothesis
Physiological processing of amyloid precursor
Amyloid precursor protein cleaved by alpha secretase releasing prducts- one of which is digested by gamma secretase
Enzymes involved in processing of amyloid
Alpha and gamma secretase
Pathophysiological processing of amyloid protein in alzheimers patients
Instead the precursor protein is cleaved by beta secretase releasing a different fragment. When this is cleaved by gamma secretase it releases amyloid beta protein and forms toxic aggregates
Where do beta amyloid protein aggregate
On cell membrane of neurones leading to immune response which destroys neurones
Secondary hypothesis to pathophysiology of alzheimers
Tau hypothesis
What are tau proteins
Soluble proteins found in axons that are important for stability and assembly of microtubules
Pathophysiology of tau hypothesis
Hyperphosphorylated tau is insoluble- tau self-aggregates to form neurofibrillary tangles that are neurotoxic. As there are less tau proteins this results in microtubule instability
Alternative less recognised hypothesis for alzheimers disease
Inflammatory hypothesis- people who have taken NSAIDS are less likely to get alzheimers
Pathophysiology of inflammatory hypothesis
Increased activity of microglial cells leads to release of inflammatory mediators and cytotoxic proteins. Get increased phagocytosis and so less neuronal protection
What drugs are given as alzheimers pharmacotherapy
Reversible cholinesterase inhbitors
Non-competitive NMDA receptor blocker
Names of reversible anticholinesterases
Donepezil- very long plasma half life
Rivastigmine
Galantamine- can act as nicotic AcH agonist
What is different about rivastigmine as anticholinesterase inhibitor for alzheimers
Inhibits butyryl cholinesterase too
