Alzheimer's disease
What is Alzheimer's disease?
Alzheimer’s disease is the most common form of dementia, accounting for more than two-thirds of all cases. Currently, Alzheimer’s affects approximately a quarter of a million Australians.
What are the symptoms of Alzheimer's disease?
The hallmark symptom of Alzheimer's disease is loss of memory, which results from early degeneration and death of neurons in the hippocampus, a structure crucially involved in memory formation. The hippocampus is also important for spatial navigation, as is the entorhinal cortex, which is the typical starting point for cell death in Alzheimer's disease.
Consistent with damage in these regions, people with Alzheimer's can be disoriented, confused and have memory problems. Subsequently, symptoms can progress to include motor difficulties and impairments in executive planning and decision making. Importantly, the timecourse of these changes is characteristic of the spread of the disease seen in Alzheimer's patients.
What causes Alzheimer's disease?
Alzheimer's results from the degeneration and death of neurons. Two proteins in particular are thought to cause the condition: amyloid-beta (Aβ) and tau. Amyloid beta is believed to cause the tau protein in neurons to become abnormal – hyperphosphorylated, with extra phosphate molecules attached to it.
The tau then moves from its usual location in the axon of neurons to the dendrites, where it causes synapses to disappear and the neurons to die. Once tau has been recruited by amyloid beta to the dendritic synapses, it appears to enable amyloid beta to trigger synapse loss and ultimately cell death.
In other words, non-toxic amyloid beta essentially recruits tau to allow the amyloid beta to become toxic; the toxicity likely occurs via a particular neurotransmitter receptor called the NMDA receptor.
The head of The Clem Jones Centre for Ageing and Dementia Research (CJCADR) at QBI, Professor Jürgen Götz, has been instrumental in developing the above theory for how tau and Aβ interact to give rise to Alzheimer’s disease.
Risk factors for Alzheimer's disease
Alzheimer's disease has some known genetic risk factors:
- APP (amyloid precursor protein) gene, which ultimately results in amyloid beta production. As mentioned earlier, Aβ appears to interact with tau protein
- Mutations in presenilin genes (which help convert APP into Aβ) and the APP gene are heritable and lead to early-onset familial Alzheimer's disease
- The ApoE4 (apolipoprotein E4) gene, which increases cardiovascular risk