6. Alzheimer Flashcards
ALzheimers areas:
cholinergic cell death in the NbM, substantia insomata, diagonal tract of broca and medial septal nulclei. PPT and Thamlus are fine - atrophy around the ventricles and connective tissue
alzheimers Symptoms
onset around 70 –> 7 yrs till death. cognitive functions go first (language reasoning and calculation) then hallucinations and delusions
protein folding disorders:
huntingtons, parkinsons, alzheimers, amylotrophic lateral sclerosis, creutzsfor-jakob syndrome
huntingtons protein
huntington
alzheimers protein
tau and amyloid beta
parkinsons protein
a-synuclein
amlylotrophic lateral scelrosis protein
superoxide dismutase (more prone to oxidative stress)
creutzsford jakob
prion
misfolding mechanisms:
tertiary structure problems causes hydrophobic residues to become exposed. these stick together and for plaques. or the protein is insoluble so cant be transported out of the cell. happens in normal people but the rate of misfolding is increased in disease states
alzheimers plaques
oligomers: amyloid beta is transported as amyloid precursor protein. cut by 3 proteolytic enzymes (a/b/g secretases). if beta amyloid 40/42 forms it is sticky and aggregates to form plaques. these cause axonal and dendritic inflammation and stimulate hyperphosphorylation of tau (in humans)
alzheimers tangles
tau proteins (helical fragments) are phosphorylated for transport. when hyperphosphorylated they form neurofibrillatory tangles which cause cell death. this mainly occurs in the temporal . lobe though plaque formation is widespread.
risk factors for Alzheimer’s
smoking, genetic predisposition and over counter antimuscarinics (e.g. antihistamines)
rats vs. humans in alzheimers
cholinergic distribution is species specific. rats respond to amyloid immunisation but humans don’t. plaques and tau related in humans but not rats.
why do we image peoples brains?
some people get cognitively impaired around 50/60 and not all go on to develop alzheimers. don’t want to waste treatment.
Alzheimers cholinesterase inhibitors
Tacarine Donezepil Rivastigmine Galantamine Memantine
