Published: 26-05-2011 00:00 | Updated: 26-11-2013 10:29

Unique Alzheimer study of four siblings

[NEWS 26 May 2011]Four siblings in a family affected by early-onset Alzheimer's have been studied by a group of researchers at Karolinska Institutet. This has been a unique opportunity to make comparative studies and to monitor the development of the disease over a prolonged period of time. Being able to monitor the disease long before diagnosis up until the death of the affected siblings has provided valuable insights into the disease's time course - something that might one day lead to improved therapies for many Alzheimer's patients.

Agneta NordbergPhoto: Ulf Sirborn

In Sweden, over 100,000 patients live with Alzheimer's disease, the most common form of dementia. Age is the largest risk factor for the disease, and while sufferers are mainly elderly, a significant number, some 10,000, are under 65. Approximately one to five per cent of all Alzheimer's patients have an early, aggressive form of the disease, which is caused by inherited mutations on three specific genes.

For the present study, which is published in The Journal of Alzheimer's Disease, the group of researchers at Karolinska Institutet monitored four siblings in a family with a history of this familial form of the disease, where two of the siblings carried one of the typical mutations and were sick, and two were non-bearers and healthy.

"By making repeated studies of these individuals we've been able to trace the development of the disease over time," says principal investigator Professor Agneta Nordberg of the Department of Neurobiology, Care Sciences and Society at Karolinska Institutet. "We've monitored the family from the time we detected the mutation on chromosome 14 of two of the siblings up until their deaths several years later."

The siblings with the mutation developed the disease before the age of 40 and died at the ages of 47 and 50. The team was able to compare the two sick siblings with the two healthy ones, and with the help of PET scans they were able to establish a decline in glucose metabolism, which is a gauge of neuronal communication, before the onset of symptoms and diagnosis. The two non-bearer healthy siblings showed neither changes in glucose metabolism in the brain nor impaired cognition.

Michael SchöllPhoto: private

"If we knew that someone was carrying one of the mutations on the three specific genes, we could examine his or her brain and see pathological changes many years before the onset of the disease, and so treatment could be started much earlier than is currently the case," says Michael Schöll, a Doctoral Student in the group that conducted the study.

"This type of study is vital to our understanding of Alzheimer's disease. The disease cannot be halted at present, and treatment is often administered too late," explains Professor Nordberg, adding that the results of this study contribute to the medical understanding of the disease and of when a future treatment is to be given in order to have an optimal impact on its course.

"Knowledge of the inherited forms of Alzheimer's, which we know are more likely to develop, can be applied to all Alzheimer's research," she continues. "The time course of Alzheimer's often begins long before diagnosis, and if we know how the disease develops in the brain we will hopefully one day be able to come up with new therapies and new drugs."


Schöll M, Almkvist O, Bogdanovic N, Wall A, Långström B, Viitanen M, Nordberg A

Time Course of Glucose Metabolism in Relation to Cognitive Performance and Postmortem Neuropathology in Met146Val PSEN1 Mutation Carriers

Journal of Alzheimer's Disease, issue 24(3), online 12 April 2011 (pre-press online version 1 February), DOI: 10.3233/JAD-2011-101563

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