Solving the mystery of Alzheimer's disease
For more than one hundred years, researchers have tried in vain to find the causes of and cures for Alzheimer's. The answer may now be found in nuclear medical imaging, which makes the functions and metabolic disturbances of the brain visible.
What is known about Alzheimer's disease is that it involves a gradual degeneration of neurons in some parts of the brain. This leads to the accumulation of beta amyloid peptides, which end up forming deposits of plaques. The deposits and the degeneration of neurons prevent messages from being transmitted to other neurons.
- Information no longer transfers fluently in the brain, and things and events from the recent past tend to be forgotten, says Professor Juha Rinne, explaining the first visible symptoms of the Alzheimer's disease.
The sooner the metabolic disturbances in the brain can be detected, the easier it is to determine the root cause from othersymptoms that emerge as the condition advances and, thus, also slow down the progress of the disease.
- This is where Positron Emission Tomography and the PET camera come in, says Rinne.
While a microscope can be used to detect the existence of plaques, it cannot be inserted into the brain of a living human being. This is why a diagnosis of Alzheimer?s cannot be confirmed with full certainty until an autopsy has been performed.
Even MRI is not sensitive enough to spot plaques. Rinne explains the difference between the two imaging techniques:
- Whereas MRI mainly shows the structure of the brain and changes in it, PET shows brain activities, that is, what is happening in the brain. The stage at which neurons no longer work properly can be detected in PET.
In a PET scan, a short-lived radioactive tracer is injected into the patient?s circulation. The blood transports the tracer to the brain, where it participates in metabolic brain processes. A PET camera and computer simulation are used to reconstruct images, which can then be compared and analysed. The tracer is safe to humans, because the radiation has a very short halflife - only a matter of minutes.
Help from nanoparticles
The latest line of research that the national PET Centre at the University of Turku is pursuing under the lead of Rinne has to do with the use of nanoparticles. Nanoparticles are extremely small - one nanometre equalling one millionth of a millimetre - which makes it easy for them to travel through the human system. The EU-funded project aims to identify, for example, a nanoparticle that could latch onto a plaque. Such a particle could be marked with a suitable radioactive isotope, after which its progress in a living human brain could be monitored with a PET camera to see where plaques exist.
-This would produce a reliable diagnosis at as early a phase as possible, says Rinne.
PET scanning can also be of use in pharmaceutical development and in the monitoring of the effects of treatment. In this case, the administered drug is marked to see whether it travels to the expected location and has the required effect.
Pharmaceutical development has made good progress with drugs that prevent the accumulation of amyloid proteins. Traditionally, patient and control groups have been monitored for years until any differences have been detected.
- PET scanning enables differences to be detected much faster and shortens the long pharmaceutical testing processes, explains Rinne.
Turku PET at the top internationally
The Turku PET Centre is an Academy of Finland Centre of Excellence and a leading research institute in its field worldwide. One of the Centre's main advantages over many other corresponding institutes is that it can tailor and produce the tracers needed for its research projects. Many of the world's imaging centres use a single tracer produced elsewhere. Such a tracer is often not suitable for all research purposes.
The PET Centre?s equipment has developed and become more versatile over the years. The start-up of a new cyclotron in the PET Centre's own facilities will mark an important step in this development.
- It will enable us to use isotopes with a halflife of only a couple of minutes. This opens up new possibilities to study metabolic dysfunctions in the brain and, for example, Alzheimer's, says Rinne.
In autumn 2008, the European Commission awarded 900,000 euro to Alzheimer's research carried out inTurku. The research project is included under the EU?s seventh framework programme and focuses on the use of nanoparticles in the diagnostics and care of Alzheimer's. The research in Turku is part of an international five-year project that involves research institutes in 15 European countries. The overall project budget totals 14.6 million euro. The project also involves the national Turku PET Centre. The subproject in Turku is led by Professor Juha Rinne, who is in charge of brain mediator research. Professor Olof Solin is responsible for radiochemistry and Adjunct Professor Merja Haaparanta for preclinical research.
Text: Timo Niitemaa
Photos: Vesa-Matti Väärä