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Current biomarkers for early Alzheimer disease (AD) include functional, structural, and protein neuroimaging as well as cerebrospinal fluid indices of amyloid beta and tau. Although these measures are increasingly valuable as predictors of conversion from amnestic mild cognitive impairment (aMCI) to AD, each is associated with variable accessibility, risk to patients, and cost to the healthcare system. These barriers have been prohibitive for large-scale assessment of potentially presymptomatic AD patients. In an attempt overcome these barriers, researchers collected peripheral blood samples from community-dwelling adults aged 70 and older. Three years later, 74 participants had aMCI or mild AD (46 incidental cases and 28 conversions during the study). The researchers compared blood test results for these individuals with those of participants who remained cognitively normal.
Ten different metabolites, including the cell membrane phospholipids phosphatidylcholine and acylcarnitine, were depleted in 53 of the participants who were cognitively impaired either at study entry or became so during the study. The same findings held when validating the 10-metabolite panel in the remaining study participants. The test had 90% accuracy in predicting which participants would develop aMCI or AD within 2 to 3 years.
— Adapted from a Physician's First Watch article published March 10, 2014.
Mapstone M et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med 2014 Mar 9; [e-pub ahead of print]. (http://dx.doi.org/10.1038/nm.3466)
Comment
This small study is provocative due to the relative ease with which peripheral blood may be accessed and systematically assessed in large populations. As the authors observe, this tool will require assessment in larger and more diverse populations before it is clinically relevant. However, these results are certainly encouraging and biologically plausible. Early intervention for neurodegenerative diseases such as AD is of critical importance to modify the disease course, and presymptomatic identification of disease would be potentially invaluable in this context.