437 research outputs found
Saliva Neurofilament Light Chain Is Not a Diagnostic Biomarker for Neurodegeneration in a Mixed Memory Clinic Population
Neurodegeneration and axonal injury result in an increasing release of neurofilament light
chain (NfL) into bodily fluids, including cerebrospinal fluid (CSF) and blood. Numerous
studies have shown that NfL levels in CSF and blood are increased in neurodegenerative
disorders and monitor neurodegeneration. Saliva is an easily accessible biofluid that
could be utilized as a biofluid measurement of Alzheimer’s disease (AD) biomarkers. In
this study, for the first time, salivary NfL was measured and compared to plasma NfL in a
consecutive cohort of patients referred to cognitive assessments. In two mixed memory
clinic cohorts, saliva samples were taken from 152 patients, AD (n = 49), mild cognitive
impairment (MCI) (n = 47), non-AD (n = 56), and also 17 healthy controls. In addition,
135 also had a matching plasma sample. All saliva and plasma samples were analyzed
for NfL, and the association between saliva and plasma NfL and CSF levels of total tau
(t-tau), phosphorylated tau (p-tau), and beta amyloid 1–42 (Ab42) were investigated. In
total, 162/169 had quantifiable levels of salivary NfL by single molecule array (Simoa).
No statistically significant differences were found in salivary NfL concentration across
the diagnostic groups, but as expected, significant increases were found for plasma
NfL in dementia cases (P < 0.0001). There was no association between saliva and
plasma NfL levels. Furthermore, saliva NfL did not correlate with CSF Ab42, p-tau,
or tau concentrations. In conclusion, NfL is detectable in saliva but does not reflect
neurodegeneration in the brain
Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring
Background
Breastfeeding protects against illnesses and death in hazardous environments, an
effect partly mediated by improved immune function. One hypothesis suggests that
factors within milk supplement the inadequate immune response of the offspring,
but this has not been able to account for a series of observations showing that
factors within maternally derived milk may supplement the development of the
immune system through a direct effect on the primary lymphoid organs. In a
previous human study we reported evidence suggesting a link between IL-7 in
breast milk and the thymic output of infants. Here we report evidence in mice of
direct action of maternally-derived IL-7 on T cell development in the offspring.
Methods and Findings
We have used recombinant IL-7 labelled with a fluorescent dye to trace the
movement in live mice of IL-7 from the stomach across the gut and into the
lymphoid tissues. To validate the functional ability of maternally derived IL-
7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets
of thymocytes and populations of peripheral T cells were significantly higher
than those found in knock-out mice receiving milk from IL-7 knock-out mothers.
Conclusions/Significance Our study provides direct evidence that interleukin 7,
a factor which is critical in the development of T lymphocytes, when maternally
derived can transfer across the intestine of the offspring, increase T cell
production in the thymus and support the survival of T cells in the peripheral
secondary lymphoid tissue
Mathematical Modelling as a Proof of Concept for MPNs as a Human Inflammation Model for Cancer Development
<p><b>Left:</b> Typical development in stem cells (top panel A) and mature cells (bottom panel B). Healthy hematopoietic cells (full blue curves) dominate in the early phase where the number of malignant cells (stipulated red curves) are few. The total number of cells is also shown (dotted green curves). When a stem cell mutates without repairing mechanisms, a slowly increasing exponential growth starts. At a certain stage, the malignant cells become dominant, and the healthy hematopoietic cells begin to show a visible decline. Finally, the composition between the cell types results in a takeover by the malignant cells, leading to an exponential decline in hematopoietic cells and ultimately their extinction. The development is driven by an approximately exponential increase in the MPN stem cells, and the development is closely followed by the mature MPN cells. <b>Right:</b> B)The corresponding allele burden (7%, 33% and 67% corresponding to ET, PV, and PMF, respectively) defined as the ratio of MPN mature cells to the total number of mature cells.</p
Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study
The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β 42 ; (ii) centrally measured cerebrospinal fluid amyloid-β 42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β 42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β 42 to amyloid-β 40 . Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer’s and Parkinson’s Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β 42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β 42 and amyloid-β 40 ) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer’s disease, while more variable results were observed for cognitively normal and non-Alzheimer’s disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference measurement procedure findings was further improved when using amyloid-β 42/40 . Agreement between Pittsburgh compound B visual ratings and Centiloids was near complete. Despite improved agreement between Pittsburgh compound B and centrally analysed cerebrospinal fluid, a minority of subjects showed discordant findings. While future studies are needed, our results suggest that amyloid biomarker results may not be interchangeable in some individuals
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