Unique case study on Alzheimer's disease

December 14, 2010

A case study from the Swedish medical university Karolinska Institutet sheds light on the pathological course of Alzheimer's disease. The brain of the first Alzheimer's patient to display amyloids demonstrable with a PET scanner has been studied, both during progression of the disease and after death.

One pathological characteristic of Alzheimer's disease is the accumulation in the brain of beta-amyloid proteins to form amyloid plaques. However, it is not known how early the plaques forms in the brain, whether they are the primary cause of the disease or what pathogenic role is played by other changes in the brain.

The very first PET scan in the world of amyloid plaque in a living patient with the amyloid-binding compound 11C-PIB was performed in 2002 by Professor Agneta Nordberg at Karolinska Institutet on a 56-year old Alzheimer's patient. The researchers then monitored the patient as the disease progressed with regular PET scans and memory tests. After the patient died, the team carried out pathological and neurochemical analyses of the brain tissue.

The combined result analyses, which are now published in the renowned neurological journal BRAIN, give a detailed picture of how Alzheimer's disease develops. For example, the results show that high concentrations of amyloid plaques were discovered at an early stage of the disease when the patient suffered slight memory loss. The levels remained unchanged during the course of the disease, in contrast to the increasingly declining energy metabolism in the brain, which was also measured using PET as the patient's memory gradually deteriorated.

One formerly unknown connection that was discovered in the study is that the greater accumulation of plaque is accompanied by a reduction in the number of neuronal nicotinic receptors in the brain. These receptors are central to memory function, and this new finding demonstrates that the receptors are affected early on in the disease development. Further, inflammatory changes were measured in brain regions with low levels of plaques, which suggest that the neuroinflammation related to Alzheimer's disease might have a different cause and evolve at different stage of the disease compared to that of amyloid accumulation. Studies on this are currently being carried out on living patients using PET technology.

Today, over 1,000 patients around the world have undergone PET scans for measuring amyloid concentrations in the brain. PIB-PET was recently recommended as the earliest clinical diagnostic biomarker for discovering Alzheimer's disease, following the diagnostic guidelines laid out by the American Alzheimer's Association. However, if clinicians are to gain further insight into the importance of these PET examinations, a follow up of the results obtained from conducted PET studies should be performed in the brain tissue of deceased patients.

"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", says Professor Nordberg. "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."
-end-
Publication: 'PET imaging and clinical progression in relation to molecular pathology in first PIB PET AD Patient', Ahmadul Kadir, Amelia Marutle, Daniel Gonzalez, Michael Schöll, Ove Almkvist, Malahat Mousavi, Tamanna Mustafiz, Taher Darreh-Shori, Inger Nennesmo & Agneta Nordberg, BRAIN, online 14 December 2010.

Journal website: http://brain.oxfordjournals.org/

For further information, please contact:

Professor Agneta Nordberg
Department of Neurobiology, Care Sciences and Society
Tel: +46(0)8-585 854 67 or +46(0)70-510 76 85
Email: agneta.k.nordberg@ki.se

Press Officer Katarina Sternudd
Tel: +46 (0)8-524 838 95
Email: katarina.sternudd@ki.se
Web: http://ki.se/pressroom

Karolinska Institutet is one of the world's leading medical universities. Its mission is to contribute to the improvement of human health through research and education. Karolinska Institutet accounts for over 40 per cent of the medical academic research conducted in Sweden, and offers the country's broadest range of education in medicine and health sciences. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine. More information on ki.se.

Karolinska Institutet

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.