neurodegeneration Flashcards
Alzheimer's disease: identify the underlying pathology, the clinical symptoms and risk factors
main risk factor for Alzheimer’s disease (leading cause of death in UK)
age
2 causes of Alzheimer’s disease
unknown (age), genetic mutations (only 8%)
genetic mutations which cause early onset of Alzheimer’s disease
APP, PSEN, ApoE
5 clinical symptoms of Alzheimer’s disease
memory loss (especially recently acquired information), disorientation and confusion, language problems, personality changes (more confused, fearful and anxious), poor judgement (e.g. dealing with money)
describe amyloid hypothesis for physiological processing
amyloid precursor protein (APP) cleaved by a-secretase -> molecule released and C83 fragment remains -> C83 fragment digested by y-secretase -> products removed
describe amyloid hypothesis for pathophysiological processing in Alzheimer’s disease
APP cleaved by B-secretase -> molecule released and C99 fragment remains -> C99 fragment digested by y-secretase releasing B-amyloid (AB) protein -> AB forms toxic aggregates (B-amyloid plaques which are not removed)
where do B-amyloid plaques aggregate
outside neurones on cell membrane, as well as other cells on CNS
describe Tau hypothesis for physiological processing
soluble tau protein present in axons, important for assembly and stability of microtubules
describe Tau hypothesis for pathophysiological processing in Alzheimer’s disease
hyperphosphorylated tau is insoluble -> self-aggregates to form IC neurofibrially tangles, which are neurotoxic and result in microtubule instability
functions of microglial cells in physiology
specialised CNS immune cells (similar to macrophages), which increase inflammatory mediators and cytotoxic proteins, increase phagocytosis, decrease levels of neuroprotective proteins
describe inflammatory hypothesis of Alzheimer’s disease
increase in microglia, causing an aberrant immunological reaction (somehow long-term NSAID use seems to be protective)
