A new method for quantifying specific amino acids in small volumes of plasma and whole blood has been developed. Based on isotope-dilution tandem mass spectrometry, the method takes only a few minutes to perform and requires minimal sample preparation. The accurate assay of both phenylalanine and tyrosine in dried blood spots used for neonatal screening for phenylketonuria in North Carolina successfully differentiated infants who had been classified as normal, affected, and falsely positive by current fluorometric methods. Because the mass-spectrometric method also recognizes other aminoacidemias simultaneously and is capable of automation, it represents a useful development toward a broad-spectrum neonatal screening method.

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Down syndrome (DS) is the most prevalent chromosomal abnormality. Early-onset dementia with the pathology of Alzheimer’s disease (AD) frequently develops in DS. Reliable blood biomarkers are needed to support the diagnosis for dementia in DS, since positron emission tomography or cerebrospinal fluid sampling is burdensome, particularly for patients with DS. Plasma t-tau is one of the established biomarkers for the diagnosis of AD, suggesting the potential value of t-tau as a biomarker for dementia in DS. The aim of this study was to assess and compare plasma levels of t-tau in adults with DS and in an age-matched control population. In this study, plasma levels of t-tau in 21 patients with DS and 22 control participants were measured by an ultrasensitive immunoassay technology, the single-molecule immunoarray (Simoa) method. We observed significantly increased plasma t-tau levels in the DS group (mean ± standard deviation (SD) = 0.643±0.493) compared to those in the control group (mean ± SD = 0.470±0.232): P = 0.0050. Moreover, age dependent correlation of plasma t-tau was only found in the DS group, and not in the control group. These findings suggest that elevated plasma t-tau levels reflect AD pathology and therefore have potential as an objective biomarker to detect dementia in adult DS.

People with Down syndrome (DS) are at high risk of developing Alzheimer disease (AD) with aging. The diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. Plasma neurofilament light chain (NfL) is one of the established biomarkers of AD, suggesting that it may be useful as an indicator of dementia in DS patients. The aims of this study were: 1) to examine whether plasma levels of NfL in DS patients are correlated with decreased adaptive behavior scores one year after sample collection, and 2) to compare plasma levels of NfL in adults with DS and an age-matched healthy control population. In this study, plasma levels of NfL in 24 patients with DS and 24 control participants were measured by the single-molecule immunoarray (Simoa) method. We observed significantly increased plasma NfL levels in the DS compared with the control group. There was a significant correlation between age and levels of plasma NfL in both groups. This age-dependent elevation was steeper in the DS compared with the control group. Moreover, elevated plasma NfL was associated with decreased adaptive behavior scores one year later, after age-adjustment. Previously reported blood-based biomarkers available in Simoa for DS, plasma total tau and phosphorylated tau, were not significantly correlated with the annual decrement of adaptive behavior scores after age-adjustment. These results suggest that plasma NfL has the potential to serve as an objective biomarker to predict dementia in adult DS patients.

We report two adult Japanese sisters with L-2-hydroxy-glutaric aciduria (acidemia), both of whom were much older (aged 57, 47 years old) than previously reported patients (from neonate to 44 years old), and who presented with differing severity. Magnetic resonance imaging revealed typical subcortical white matter lesions in both cases and showed brainstem atrophy and thickness of the calvarium in the elder sister. L-2-Hydroxyglutaric acid levels were increased in urine, plasma, and cerebrospinal fluid. These cases suggest that organic acid analysis is necessary even in elderly patients who seem to have neurodegenerative disorders.

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Recent studies have shown that cells from bone marrow (BM) can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved remain unknown. We performed BM transplantation in acid alpha-glucosidase (GAA) knockout mice, a model of glycogen storage disease type II, and our observations suggested that the BM cells contribute to skeletal muscle fiber formation. Furthermore, we showed that most CD45+:Sca1+ cells have a donor character in regenerating muscle of recipient mice. Based on these findings, CD45+:Sca1+ cells were sorted from regenerating muscles. The cell number was increased with granulocyte colony-stimulating factor after cardiotoxin injury, and the cells were transplanted directly into the tibialis anterior (TA) muscles of GAA knockout mice. Sections of the TA muscles stained with anti-laminin-alpha2 antibody showed that the number of CD45+:Sca1+ cells contributing to muscle fiber formation and glycogen levels were decreased in transplanted muscles. Our results indicated that hematopoietic stem cells, such as CD45+:Sca1+ cells, are involved in skeletal muscle regeneration.