For the first time the brain of a patient with Alzheimer's disease who displayed detectable amyloids with a PET scanner was regularly scanned as his disease progressed, and then his brain was analyzed after he died, researchers from the Karolinska Institutet, Sweden, reveal in the medical journal Brain. The authors say their study reveals important data on the pathological course of Alzheimer's disease.
Alzheimer's disease, also known as SDAT (Senile Dementia of the Alzheimer Type), or simply Alzheimer's, is a progressive neurologic brain disease which leads to irreversible loss of neurons and intellectual abilities, including reasoning and memory. Eventually, the patient is unable to function professionally, socially or independently. Plaques or tangles develop within the structure of the brain during the course of the disease, causing brain cells to die. The accumulation in the brain of beta-amyloid proteins form amyloid plaques.
The authors explain that we do not know how the plaques form in the brain in the early stages of the disease. We don't even know whether the plaques are the primary cause of Alzheimer's, and what the pathogenic impact might be of other alterations in the brain.
In 2002, Professor Professor Agneta Nordberg carried out the first PET scan ever of amyloid plaque on a living patient with 11C-PIB, an amyloid-binding compound. It was performed at the Karolinska Institutet on a patient with Alzheimer's disease; he was 56 years old at the time. The progression of his disease was tracked with periodic PET scans and memory tests. After death, the researchers performed neurochemical and pathological analyses of his brain tissue.
Their findings provide us with a detailed picture of how Alzheimer's develops. During the early stages of the disease, when the patient experienced only slight memory loss, high concentrations of amyloid plaques were detected. Amyloid plaque levels, in fact, did not change as the disease progressed, right until the patient died. However, the PET scans were able to show that his brain's metabolism declined with time. The decline in brain metabolism occurred in parallel to his rate of memory loss.
The scientists also discovered that an accumulation of plaque is accompanied by a fall in the brain's neuronal nicotinic receptors, which are key for the proper functioning of memory. We now know that these receptors are affected during the early stages of Alzheimer's.
The scientists also believe that inflammation of parts of the brain of a patient with Alzheimer's may have a different cause and occur at different times from the accumulation of amyloid. They found brain inflammation in areas of the brain with low levels of plaques. The authors inform that further research with living patients on this subject is currently underway.
Over 1,000 individuals have undergone PET scans to see what amyloid concentrations they have in their brains. The American Alzheimer's Association in its latest diagnostic guidelines includes PIB-PET as a recommended early clinical diagnostic biomarker for discovering Alzheimer's disease.
In order to fully understand the importance of the PET scans, a follow-up examination of brain tissue should be carried out after the patient has died, the researchers wrote.
Professor Nordberg said:
- "If we combine different examinations, we will be able to affirm that complex changes take place at the same time in the brain during the development of Alzheimer's disease. Our study shows that new, modern imaging technology known as molecular imaging makes it possible to discover the disease at an early stage. This opens up new opportunities for early diagnosis and for understanding the causes of the disease and identifying patients who can be expected to respond well to future Alzheimer's therapy."
Ahmadul Kadir,Amelia Marutle, Daniel Gonzalez, Michael Schöll, Ove Almkvist, Malahat Mousavi, Tamanna Mustafiz, Taher Darreh-Shori, Inger Nennesmo and Agneta Nordberg
Brain (2010) doi: 10.1093/brain/awq349
Written by Christian Nordqvist