Dementia Flashcards
Define dementia
A broad category of brain disease that causes long term and gradual decrease in memory, communication and ability to carry out daily activities
Risk factors of dementia?
Age Genetic pre-disposition Family history Downs syndrome Vascluar risk factor Cognitive inactivity Environment Depression
What occurs in a patient with Alzheimers with their brain?
Extreme shrinkage of the hippocampus
Extreme shrinkage of the cerebral cortex
Severely enlarged ventricles
What genes for early onset?
APP
PSEN1
PSEN2
What genes for late onset?
APOE4
apolipoprotein
What is an amyloid precursor protein?
Transmembrane protein with a number of roles e.g. neural proliferation, migration, differentiation, plasticity and synaptogenesis
What are mutations in APP associated with?
Familial form of early-onset Alzheimer’s disease as well as cerebral amyloid angiopathy (CAA)
What do mutations in APP generally increase?
AB (beta) production
What decreases AB production?
A673T
What is the amyloid precursor protein (APP) cleaved by?
alpha-secretase
B-secretase
gamma-secretase
Which pathways is APP cleaved in?
Non-amyloidogenic pathway (alpha secretase and gamma secretase) amyloidogenic pathway (B-secretase + gamma secretase)
What does the amyloidogenic pathway lead to the production of?
Ab 40-42
What are the subunits of gamma secretase?
Presenilin 1 (PSEN1) and presenilin-2 (PSEN2)
What enzyme is responsible for AB generation?
aspartyl protease
Which subunit of gamma secretase is more common in early-onset Alzheimer’s disease?
PSEN1
What is ApoE?
lipoprotein
What is ApoE involved in?
cholesterol metabolism
What alleles do ApoE have?
ApoE2
ApoE3
ApoE4
What does ApoE4 show to decrease?
Decrease clearance of extracellular AB
What is a Tau protein?
microtubule-associated protein
What is the function of Tao?
Role in microtubule stabilisation and axonal transport
how is tau-microtubule binding maintained?
Co-ordinated actions of kinases and phosphatases
Phosphorylation of Tau regulates its activity to bind to icrotubules
What does hyperphosphorylation of Tau result in?
Formation of neurofibrillary tangles - primarily composed of paired felical filaments
What does acetylcholine bind to?
Nicotinic
Muscarinic receptors
