A new blood borne marker for Alzheimer's disease?

Dementia News 75, September 2007

Last August Molecular Psychiatry has published a paper by Lanni et al. suggesting the existence of a novel Alzheimer's disease marker. The data presented are the result of a long term collaboration between two Italian research groups, of the universities of Pavia and Brescia, and one of the results of the national research program supported by the ministry of the university (Grant nr. 2005051707) and coordinated by S. Govoni. It may be interesting to explore some of the backstage aspects of this research.

The cooperation with the group headed by M. Memo (Brescia) on this particular topic started several years ago. At that time we were studying the characteristics of the fibroblasts from control and AD patients, a line of research started back in 1993 that led us in the late nineties, together with other research groups worldwide, to conclude that fibroblasts were a tissue with a great potential to study biochemical defects underlying the disease, but were not suitable to be easily used as biological markers for diagnosis because of the inherent difficulties and time consuming procedures needed to work with them. In 2000-2002 we were investigating the response of AD fibroblasts to noxious stimuli and, to our surprise, we discovered that the cells derived from patients were less sensitive to hydrogen peroxide than control cells. Taking advantage of the experience of the M. Memo group on the study of p53 and of its role in cell cycle we were able to demonstrate that the resistance of AD fibroblasts was due to the selective impairment of the p53 cell death in AD fibroblasts (Uberti D et al. 2002).

In the next four years we were able to show that the resistance of AD fibroblasts was due to a conformational mutation of p53 (Uberti D et al. 2006). At the same time, taking advantage of the fact that p53 is also present in peripheral circulating blood cells, we developed a quantitative method able to detect conformational mutated p53 using a small (3 ml) blood sample and a FACS (Fluorescence Activated Cell Sorter), an instrument available in several clinical settings. Using this method we analyzed a reasonably large number of AD patients (104 patients with AD, 92 age-matched control), as reported in the Molecular Psychiatry paper, finding that mononuclear cells from AD patients express a higher amount of mutant-like p53 compared to non-AD subjects, thus supporting the study of conformational mutant p53 as a new putative marker to discriminate AD from non-AD patients. We also observed a strong positive correlation between the expression of p53 and the age of patients.

As many other peripheral markers of AD, also the one we studied awaits independent confirmation by other research groups. On the other hand it has the advantage of being the first one that can be studied using a small blood sample and techniques that are familiar and available to the clinics, and this will help to answer to the question whether or not this is a new easy to measure diagnostic marker, in a reasonable time frame.


prof. Stefano Govoni
Department of Experimental and Applied Pharmacology, University of Pavia, Italy

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