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IBSA Foundation_Alzheimer's disease
Paolo Rossi Castelli03 Aug 20233 min read

A test to detect Alzheimer's 20 years ahead of time

Cutting edge research in the United States. 32 blood proteins have been identified that seem capable of predicting the onset of Alzheimer’s. Such an early diagnosis would be extremely valuable for enabling the safe use of two new drugs that have recently been approved.

Finding a simple, reliable and relatively inexpensive way to diagnose Alzheimer’s dementia when it is beginning to develop but is still undetectable at the clinical level is a goal that, until now, has seemed practically unachievable (the only techniques used at present are extremely invasive, like spinal taps, or highly sophisticated, such as particular types of radiological or brain imaging, which are not within everyone’s means). 
However, the need for early diagnosis is becoming increasingly pressing, including in light of the approval in the United States of two new drugs (monoclonal antibodies)—Lecanemab and Aducanumab, and probably a third as well in coming months—which seem to be effective against Alzheimer’s, but which also appear to be extremely delicate and dangerous, requiring a definite and precise diagnosis before use. 
Now this goal is closer to being attainable, thanks to a very important study that lasted over 25 years, whose results have just been published by neurologists and researchers from the National Institute on Aging and a number of American universities in the journal Science Translational Medicine

Alzheimer’s diagnosis: a biological “signature” has been found

This study involved the analysis of over 4,800 proteins found in the plasma (the part of the blood without cells in it) of 11,000 people between 45 and 65 years of age. The concentration of these proteins was carefully monitored for a quarter of a century. Specifically, the researchers attempted to establish whether, among those 4,800 proteins, any showed variations that could enable a very early diagnosis of Alzheimer’s dementia being bound to develop with time. 

And that is, as a matter of fact, what they found. The researchers discovered not one, but a full 32 proteins that change in specific ways in people who will develop the disease in the future, meaning that these could constitute a “biological signature”, capable of acting as a marker. Twelve of these molecules also have a very close relationship to other proteins present in the cerebrospinal fluid (which surrounds the brain and the spinal cord), which are already considered to be, in one way or another, markers for the disease, because they are indicators of neuroinflammation and neurodegeneration.

A focus on 9 molecules in particular

A number of the 32 proteins/markers seem able to predict the disease about 20 years before the appearance of symptoms, and others, associated with blood clotting, 10 years before.
 If we wished to select only the most helpful from a diagnostic perspective, the number falls to 9. These include a protein called SERPINA3, against which specific monoclonal antibodies, used for research purposes, already exist (because it is involved in other diseases). 
Tests will continue, in order to understand once and for all whether an analysis of plasma proteins is truly able to offer clear answers, but if it is, our approach to dementia could change significantly, especially from the point of view of early diagnosis and population screening (which could be conducted beginning at a specific age), which are currently not possible. It would also, as we have mentioned, allow for an easier and more “targeted” use of the new drugs just approved in the U.S., around which many uncertainties still exist, especially when they are not administered during the truly early stages of Alzheimer’s disease.


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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.