Alzheimer's, so obesity accelerates it: blood tests warn even before symptoms

Not only altered metabolism with an increased likelihood of developing type 2 diabetes, increased cardiovascular risk, earlier onset of arthrosis and joint disease, increased risk of sleep apnoea and breathing difficulties. Obesity may also represent a subclinical accelerator for those who will develop Alzheimer's disease, acting well before there is any clear sign of damage, even on the most sophisticated radiological examinations such as PET. Pointing out how and to what extent obesity could speed up the trajectory leading to neurodegeneration, using blood tests that act as biomarkers, is the first research showing that in the presence of this pathological condition, even up to 95 per cent faster increases in biomarkers of neurological disease can be observed (compared to non-obese people). This is shown by the first study to demonstrate the relationship between obesity and Alzheimer's based on markers detectable from blood. The research was co-ordinated byCyrus Raji and Soheil Mohammadi, from the Neuroimaging Labs Research Center of the Mallinckrodt Institute of Radiology (MIR) at the Washington University School of Medicine in St. Louis, and was presented at the congress of the Radiological Society of North America.

The study took an in-depth look at information from 407 volunteers who had been followed for five years as part of the Alzheimer's Disease Neuroimaging Initiative, with analysis of scans using both Positron Emission Tomography (PET) scans for amyloid substance and blood samples. PET scans make it possible to verify the accumulation of beta-amyloid protein in the brain in the form of amyloid plaques, a typical feature of the disease. Instead, Alzheimer's-related proteins such as pTau217 (a biomarker used in the diagnosis and monitoring of the disease), neurofilament light chain (NfL), i.e. protein residues from severely damaged neurons, and GFAP, a protein mainly expressed in astrocytes (cells that support and protect neurons in the brain and spinal cord), were searched for in blood.

By analysing all these parameters and combining them with the Body Mass Index (BMI) over time, it was seen that at the beginning of the study, a higher BMI was associated with lower levels of markers in the blood and a lower overall amyloid load in the brain. The reason? According to Mohammadi, 'the reduction in BBM blood biomarkers in obese individuals would be due to dilution due to higher blood volume'. But it is another fact that is worrying. Over the years, both biomarker indications for Alzheimer's disease and PET brain scans showed more Alzheimer's-related indications in obese individuals than in non-obese individuals. Obese people experienced a more rapid increase in plasma pTau217 levels from 29% to 95%. Obesity at the start of the study was also associated with a 24% faster increase in blood levels of NfL and a slightly faster increase in amyloid accumulation. In general terms, Raji points out that according to these results, blood tests may be more sensitive than PET scans, at least in the early stages of biochemical changes, to indicate the influence of obesity on Alzheimer's-related brain changes. 'We can monitor the predictive influence of obesity on the increase in blood biomarkers with greater sensitivity than PET,' the expert comments.

'The study reinforces the evidence of a strong association between obesity and Alzheimer's disease and shows that the relationship can be investigated by means of blood biomarkers, which are easily accessible and applicable on a large scale in clinical trials, even in the phases preceding clinical onset,' comments Mario Stampanoni Bassi, neurologist at IRCCS Neuromed. The approach adopted, it must be said, is also of interest for the study of other neurodegenerative diseases, such as Parkinson's and multiple sclerosis. Above all, the research makes it possible to explore avenues of knowledge that confirm the importance of inflammatory mechanisms as a possible 'fuel' for the pathological processes of neurodegeneration. 'The mechanisms underlying the link between obesity and Alzheimer's disease are complex, but converging data indicate a central role for neuroinflammation,' the expert confirms. It is a process aggravated by obesity, capable of altering amyloid metabolism and the function of neurons and astrocytes, key cells in the pathogenesis of Alzheimer's'.