Alzheimer disease Flashcards
What is alzehimer’s disease?
A neurodegenerative disease and type of dementia that affects memory, thinking and behaviour.
What is early-onset AD?
Onset before age 65 (as young as 30)
3 genes implicated (all are autosomal dominant):
1. amyloid precursor protein gene (APP) - codes for APP cell membrane protein thought to play a role in synaptic development, neuronal plasticity and cell signalling.
2. presenilin-1 gene (PSEN1)
3. preseneilin-2 gene (PSEN2)
Both PSEN1 and PSEN2 code for proteins involved in the metabolism of APP - mutation cause an increase in the production of b-amyloid peptide
What is late-onset AD?
- Develops after 65 (average onset is 80)
- having a parent or sibling increases risk 3-fold
- having the apolipoprotein EF (apoE4) gene increases risk
ApoE = protein in lipoproteins which carry TGs and cholesterol to target cells. APoE4 binds to b-amyloid peptide and is found in plaques.
What are the 4 components of pathophysiologic changes in brain structure in AD?
- amyloid (neuritic or senile) plaques
- neurofibrillary (tau) tangles
- cerebral atrophy
- decreased acetylcholine production
Describe amyloid plaques.
- APP (amyloid precursor protein) normally cleaved by secretase to produce soluble fragments that are released outside the neuron
- fragments normally broken down and eliminated
- improper cleavage produces b-amyloid peptide = insoluble and clumps together forming plaques that surround neurons (extracellular)
- plaques (also contain APoE4) = impair connection between neurons causing neuron degeneration & contribute to neuroinflammation = involves microglia (phagocytic cells of nervous tissue) which release free radicals found in close proximity to plaques
What are neurofibrillary tangles?
Tau proteins bind and stabilize microtubules in neurons (internal support).
In AD Tau proteins are altered = unable to bind to microtubles and form tangles (intracellular) that resist breakdown
Microtubules destabilize
