Alzheimer's disease Flashcards
Main risk factor for Alzheimer’s disease
Age (also fam hx)
Symptoms of AD
memory loss (recent events), disorientation, confusion, language problems, personality changes = fear, anxiety, anger, poor judgment
3 hypotheses for AD pathophysiology
Beta-Amyloid plaques
Tau protein tangles
Inflammation
Normal amyloid precursor protein (APP) physiology
APP, alpha secretase, gamma secretase present in cell membrane.
alpha secretase cleaves APP, releasing sAPPa, c83 remains.
Gamma secretase cleaves c83 into other products
Pathological APP metabolism
APP, beta secretase and gamma secretase present in cell membrane.
Beta secretase cleaves APP to release sAPPbeta, C99 remains
Gamma secretase cleaves C99 releaseing beta amyloid, which accumulates extracellularly
Briefly describe Beta amyloid protein hypothesis of AD
Accumulation of beta-amyloid into EXTRAcelullar plaques due to pathophysiological metabolism of APP -> neurotoxic
Briefly describe Tau tangle hypothesis of AD
Hyperphosphorylated tau proteins form INTRAcellular tangles -> neurotoxic
Normal function of tau proteins
They SOLUBLE proteins in axon, are incorpirated into microtubule structure to stabilise them and aid assembly.
Pathophysiology of tau proteins in AD
Tau proteins hyperphosphorylated, become INSOLUBLE, self-aggregate producing INTRAcellular neurofibrillary tangles -> neurotoxic.
Also cause microtubule instability
Explain Inflammatory hypothesis of AD
Microglia produce more inflammatory mediators and cytotoxic proteins, decreased neuroprotection, increased phagocytosis
Normal role of microglia
Resident macrophages of the brain
Principle of AD drugs
Used to alleviate and improve SYMPTOMS, have no effect on pathogenicity
Drugs used in AD
Donepezil Rivastigmine Galantamine Memantine NB must all be able to cross BBB bc act centrally
Donepezil MOA + PK
reversible antiAChE, long t1/2
Rivastigmine MOA + PK
Pseudo-reversible antiAChE/BChE, t1/2=8hrs
