Researchers in China identified 875 metabolites that differed in the blood plasma of patients newly diagnosed with late-onset Alzheimer's disease who had not yet started any treatment, compared with cognitively healthy peers, according to a study published in Frontiers in Aging Neuroscience. The changes were concentrated among lipids, fatty acids such as dodecanoic acid and arachidonic acid, and amino acids such as L-arginine and L-leucine, with 227 of the metabolites elevated and 648 reduced.
The cross-sectional, case-control study compared plasma from 35 outpatients with late-onset Alzheimer's disease, tested before treatment began, with 35 sex-matched cognitively healthy adults. Pathway analysis linked the metabolite changes to fatty acid and amino acid metabolism, GABAergic synapse signaling, and intestinal immune network pathways. The same patients also had higher blood levels of the inflammatory proteins TNF-alpha and IL-17, lower levels of IL-9, and blood patterns of tau and amyloid, already used as indicators of Alzheimer's pathology, that moved in the direction expected for the disease. The authors describe this as evidence that peripheral metabolic and immune changes move together in people with the disease, though they stop short of saying one causes the other.
The study's own authors caution that their findings are a starting point, not a conclusion: they describe the results as providing "a foundation for biomarker development and therapeutic targeting in late-stage disease, pending independent validation." The 35-versus-35 sample is small, came from a single outpatient population in China, and captures a single blood draw at one point in time, so it cannot show whether the metabolic changes came before or after the disease process began, or whether they would look the same in other populations.