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J Neuropathol Exp Neurol. 2014 Jul;73(7):640-57. doi: 10.1097/NEN.0000000000000091.

Metabolomics of human brain aging and age-related neurodegenerative diseases.

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From the Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, Lleida (MJ, MP-O, AN, RP); Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, Biomedical Research Institute of Bellvitge, L'Hospitalet de Llobregat, Barcelona (IF); and Center for Biomedical Research on Neurodegenerative Diseases, Spanish Institute for Health Carlos III, Madrid (IF), Spain.


Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

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