Beta- amyloid deposition and apolipoprotein E interaction
Mechanism
- After TBI → Aβ concentrations and apolipoprotein E (ApoE) concentration drops → Apolipoprotein E (ApoE) used to form ApoE-lipid complexes to repair neurons → later on there is an increase production of ApoE → for whatever reason which lead to formation of ApoE-Abeta complexes that deposit intra- axonal in the brain parenchyma → lead to neuronal damage → poorer recover of TBI and accelerated degen of brain (Alzheimer)
- Long- term follow- up of patients with TBI also correlated with incidence of Alzheimer’s disease,
- ApoE isotype as a key predictor.
- TBI is shown to trigger pathological production and accumulation of amyloid- (Aβ) peptides
- Cleavage of amyloid precursor protein (APP) produces
- Apolipoprotein E (ApoE)
- ApoE ε4
- Carries greater risk for Aβ burden
- ApoE ε4 binds the least avidly to cytoskeletal proteins that would promote neurite growth and neuroprotective effect.
- ApoE ε4 binds more avidly to Aβ and promotes aggregation into amyloid fibrils.
- 6 months after TBI
- 57% of patients have unfavourable outcome (GOS: dead, vegetative state, or severe disability)
- ApoE ε3
- (More frequent)
- Reduce the risk for Aβ burden
- ε2
- (Rare)
- Reduce the risk for Aβ burden.
- 6 months after TBI
- 27% of patients have unfavourable outcome
- Neuroprotective against cerebral ischaemia,
- Intraventricular infusion of ApoE reduced neuronal damage after ischaemia in animal models via clearance of lipid and cholesterol debris.
- Anti-inflammatory
- Effects through downregulation of microglia and cytokine release
- Aβ
- Higher risk
- Types of injury
- DAI
- Intracranial microdialysis measured high levels of Aβ in patients with DAI compared to focal injuries
- Contusional and pericontusional regions