by Mark Mapstone, PhD, Professor of Neurology
By now, most Alzheimer’s researchers have seen the writing on the wall. If we are to realize successful treatments or even a cure for Alzheimer’s disease we must turn our attention from the study of patients who have already developed dementia to those who are in the earliest stages of the disease where presumably, the brain pathology is less extensive and possibly more receptive to intervention. This shift to studying preclinical disease will allow us to determine exactly what the earliest brain changes are and hopefully, develop means to treat, reverse, or even prevent these changes years before the symptoms become apparent.
But here’s the rub. Alzheimer’s disease is identified by clinical examination showing cognitive decline that affects daily function. How do we find people who don’t have cognitive symptoms, but do have the underlying brain disease and will develop symptoms in the future? The answer, for now, is to identify a biological marker – a biomarker – of future risk that doesn’t rely on clinical symptoms. Cardiologists have risk biomarkers for heart disease like low density lipoprotein cholesterol (LDL-C), triglycerides, even the blood pressure. Why don’t we have good biomarkers for AD risk? We need a blood pressure cuff for the brain.
A group led by Prof Francis Martin at the University of Central Lancaster in the UK may have brought us closer to a biomarker for preclinical Alzheimer’s disease. In their study, the research team analyzed blood samples from 347 adults with Alzheimer’s disease or other neurodegenerative dementias and 202 age-matched healthy control subjects. They used a technique called vibrational spectroscopy, which takes advantage of the fact that molecular bonds between different atoms vibrate at different frequencies. Using this approach, they were able to measure the abundance of broad classes of molecules such as proteins, lipids, nucleic acids, etc. in the blood samples of the study subjects. This method of identifying the composition of molecules in the blood is low cost and safe, with the main risk coming from a standard blood draw. Thus, this technology could be implemented at point-of-care locations such as local clinics or primary care offices instead of sending samples to a central laboratory for analysis.
The researchers found that blood from Alzheimer’s patients had greater amounts of specific proteins and decreased amounts of specific lipids compared to blood from the control subjects. Unfortunately, vibrational spectroscopy does not allow for the identification of the specific proteins and lipids, but the researchers speculate that based on the type of protein bonds identified that these may be contained in amyloid protein, which forms the amyloid plaques in Alzheimer patients’ brains. They further suggest that the lipid bonds may be contained in the kinds of lipids that make up brain cells and are decreased as a result of brain cell loss in Alzheimer’s disease. While these speculations are in line with what we know about Alzheimer’s disease brain pathology, the proteins and lipids do need to be positively identified in future studies.
The researchers found that these molecular abundance differences were useful for telling which subjects had Alzheimer’s disease and which did not. They report that the relative amounts of the lipids and proteins provided 70% sensitivity and specificity for classifying the subjects. Sensitivity and specificity increased to 86% if the subject had another genetic risk factor for Alzheimer’s disease, the APOE ε4 allele.
Future studies will need to demonstrate that this approach has utility in the preclinical stage of the disease where presumably, the protein and lipid differences between preclinical Alzheimer’s subjects and controls may be much smaller. The results of this study are encouraging, but perhaps the technique of vibrational spectroscopy is the real star here. This approach offers significant advantages to other laboratory based methods including the seeming ease of implementation as a low cost, point-of-care technique for measuring the molecular composition of blood.
Read more about the study on CNN.com >
