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Biomarkers help predict the risk of Alzheimer’s in patients with mild cognitive impairment

A large multicentre study has shown that CSF (cerebrospinal fluid) biomarkers can be used to predict, with good accuracy, as to which patients with mild cognitive impairments will develop Alzheimer’s disease. The biomarkers used are microtubule-associated proteins that are abundant in CNS neurons as well as beta amyloid, which is a peptide that forms brain plaques in people with Alzheimer’s disease. Changes in the concentrations of these proteins can be used to identify incipient AD.

Prof. Dr. Johannes Schröder, Head of Gerontopsychiatric Research, Centre for Psychosocial Medicine, University Hospital Heidelberg © private

The multicentre study, coordinated by Dr. Niklas Mattsson, University of Gothenburg, Sweden, involved the Department of Gerontopsychiatry at the University Hospital of Heidelberg (Director: Professor Johannes Schröder, principal investigator: Dr. Elmar Kaiser) as well as 11 additional centres in Europe and the USA. The results were recently published in the "Journal of the American Medical Association".

Alzheimer's disease (AD) is the most common cause of dementia, affecting more than 15 million people worldwide. The onset of any kind of dementia is characterised by mild memory disorders. Cognitive impairment is a syndrome characterised by a loss of intellectual capacities, such as memory and flexibility beyond the age-adjusted norm, but not severe enough to fulfil the criteria for dementia. In order to improve Alzheimer's disease treatment, it is necessary to initiate treatment very early on in the disease process, before the neurodegenerative processes are too severe.

Reliable biomarkers in the cerebrospinal fluid

In Alzheimer’s patients, tau proteins have been reported to form aggregates, so-called neurofibrils in the brain. Higher tau concentrations are found in the cerebrospinal fluid in people with damaged neurons, phosphorylated tau proteins are specifically found in Alzheimer’s patients. Another typical finding in the cells of brains affected by Alzheimer’s disease is neuritic plaques, which consist mainly of beta amyloid peptides. The beta amyloid concentrations are therefore lower in the CSF.

Deposition of tau protein fibrils in a mouse brain © ZMBH Heidelberg

The study has shown that these biomarkers are able to correctly identify 83 per cent of patients with mild cognitive impairments and who will later on develop Alzheimer's disease. The study involved 1,200 patients. Initially, 529 AD patients were compared with 304 controls to identify cut points. 750 individuals with mild cognitive impairment were subsequently followed for at least two years, or until their symptoms had progressed to clinical dementia.

Not yet fit for clinical routine

“Although the predictive power of the biomarkers is excellent, these tests are not yet appropriate for routine clinical use because it is not currently possible to prevent, or at least delay, Alzheimer’s disease,” write the authors of the study. Nevertheless, the biomarkers are useful screening values, enabling the close clinical monitoring of patients at risk of developing Alzheimer’s. In addition, the tests help select those patients that are eligible for treatment with newly developed drugs.

Further information:

Dr. med. Elmar Kaiser or Prof. Dr. med. Johannes Schröder
Department of Gerontopsychiatry
Hospital for General Psychiatry
University Hospital of Heidelberg
Voßstr. 4
69115 Heidelberg
Tel: +49 (0)6221 / 56 44 48
E-mail: Elmar.Kaiser(at)med.uni-heidelberg.de

CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment, Niklas Mattsson, Henrik Zetterberg, Oskar Hansson, et al., JAMA, 2009, 302(4): 385-393.
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