Alzheimer's is typically thought of a disease that affects the elderly, but ten per cent of people with Alzheimer's have the early-onset form and are under the age of sixty-five. While about 50% of early-onset Alzheimer's cases do not show specific mutations, there is a strong genetic linkage. Mutation positive for genes APP, PS1 or PS2 is a solid confirmation of the diagnosis. It is possible that those without these mutated genes may have other mutated genes that also cause the disease. Sadly, the genetic element means that any offspring may have inherited the mutated form of a gene. This can only be diagnosed by genetic screening.
2012: Current drugs for treating Alzheimer's dementia can slow its progression for a significant period of time but are not a cure. The sooner someone is diagnosed and put on medication the more likely they will be able to benefit if better treatments become available. Examples are Aricept (boosts cholinergic functioning) and Namenda.
Diagnosis: finding amyloid plaques and/or neurofibrillary tangles in the brain.
The cognitive deficits - the symptoms of dementia - occur before the plaques form and neurons die.
In the brain of someone with Alzheimer's, there is too much of a soluble protein called amyloid-beta 42. Either too much is made or not enough is cleared away. When too much is present, these individual little peptides stick together and form small oligomers. These gluey oligomers of amyloid-beta 42 lodge in synapses - the spaces between neurons - and interfere with synaptic transmission, the ability of neuron number one to 'talk' to neuron number two. And when this happens, new information isn't learned. Or old information can't be accessed. Synaptic plasticity suffers. Over time because this synapse isn't working properly and because of inflammation and other problems, that nerve axon terminal will retract. Eventually, unable to function, the neuron will die, leaving behind empty space (the atrophy seen on MRI scans) and possibly a heap of amyloid-beta 42 in an amyloid plaque.
The degree of dementia correlates only with synapse dysfunction, not with neuronal loss, not with number of plaques, not with atrophy on an MRI scan.
The cure (disease altering) treatments will need to:
- impede production of amyloid-beta 42,
- increase clearance of already produced amyloid-beta 42,
- prevent amyloid-beta 42 from sticking to itself so it can't form oligomers, or
- rip these already formed oligomers apart.
If such treatments are found, the hope is that people suffering from symptoms of dementia can be treated before they've experienced any neuron death. If the synapses are fixed, neurotransmission can work again.
Source: Still Alice by Lisa Genova (Simon & Schuster, 20012)
