An international team of scientists found that a unique “signature” of three proteins present in the spinal fluid of 90 per cent of people with Alzheimer’s disease was 100 per cent successful in identifying which patients in another group with mild cognitive impairment (MCI) went on to develop Alzheimer’s, opening the possibility that such a test could lead to earlier diagnosis of the disease.

You can read how Dr Geert De Meyer, Ghent University in Belgium, and colleagues in the Alzheimer’s Disease Neuroimaging Initiative conducted the research that led to these findings in the August issue of Archives of Neurology.

The authors wrote in their background information that while we know that the process that leads to Alzheimer’s disease starts at least 10 years before symptoms emerge, we don’t know precisely what to look for.

One thing scientists have been focusing on is concentrations of three proteins found in cerebrospinal fluid (CSF) as possible biomarkers of the disease: CSF beta-amyloid protein 1-42 (CSF Aß1-42), total CSF tau protein and CSF phosphorylated tau181P (P-Tau181P).

The challenge, wrote the authors, is showing how we might use these concentrations as “true indicators of the pathogenic process at an early stage”.

For this study, using information from the US Alzheimer’s Disease Neuroimaging Initiative they analyzed data on 102 older adults with Alzheimer’s disease (AD), 200 who had mild cognitive impairment (MCI) and 114 who were cognitively normal.

Then, without considering who had AD, MCI or were cognitively normal, they developed a “biomarker mixture model” of the three proteins where one profile or “signature” of the three proteins was presumed to be a match to Alzheimer’s disease and the other to a “healthy” status.

The AD signature was found in 90, 72 and 36 per cent of patients in the Alzheimer’s disease, MCI and cognitively normal groups respectively.

De Meyer and colleagues then validated the signatures in two further data sets. One was a group of 68 cases of Alzheimer’s that had been confirmed by autopsy. The AD signature matched 94 per cent of them. In the other data set of 57 patients with MCI who were followed for 5 years the AD signature matched 100 per cent of the patients that went on the develop Alzheimer’s.

These results suggest that the model was able correctly to classify patients with AD without reference to their clinical diagnosis.

The researchers said the fact they found the AD signature in 36 per cent of the cognitively normal group suggest that signs of Alzheimer’s, the disease pathology, is “active and detectable earlier than has heretofore been envisioned”.

They concluded that these findings support the view that the current criteria for diagnosing Alzheimer’s disease be revisited, “at least as far as early-stage Alzheimer’s disease is concerned”.

“Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People.”
Geert De Meyer; Fred Shapiro; Hugo Vanderstichele; Eugeen Vanmechelen; Sebastiaan Engelborghs; Peter Paul De Deyn; Els Coart; Oskar Hansson; Lennart Minthon; Henrik Zetterberg; Kaj Blennow; Leslie Shaw; John Q. Trojanowski; for the Alzheimer’s Disease Neuroimaging Initiative.
Arch Neurol, Aug 2010; 67: 949 – 956.
DOI:10.1001/archneurol.2010.179

Written by: Catharine Paddock, PhD