Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe.

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.

In vivo measures of tau burden are associated with atrophy in early Braak stage medial temporal lobe regions in amyloid-negative individuals.

INTRODUCTION: It is unclear the degree to which tau pathology in the medial temporal lobe (MTL) measured by 18F-flortaucipir positron emission tomography relates to MTL subregional atrophy and whether this relationship differs between amyloid-ß-positive and amyloid-ß-negative individuals. METHODS: We analyzed correlation of MTL 18F-flortaucipir uptake with MTL subregional atrophy measured with high-resolution magnetic resonance imaging in a region of interest and regional thickness analysis and determined the relationship between memory performance and positron emission tomography and magnetic resonance imaging measures. RESULTS: Both groups showed strong correlations between 18F-flortaucipir uptake and atrophy, with similar spatial patterns. Effects in the rhinal cortex recapitulated Braak staging. Correlations of memory recall with atrophy and tracer uptake were observed. DISCUSSION: Correlation patterns between tau burden and atrophy in the amyloid-ß-negative group mimicking early Braak stages suggests that 18F-flortaucipir is sensitive to tau pathology in primary age-related tauopathy. Correlations of imaging measures with memory performance indicate that this pathology is associated with poorer cognition.

Non-tunneled versus tunneled dialysis catheters for acute kidney injury requiring renal replacement therapy: a prospective cohort study.

BACKGROUND: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is associated with high morbidity, mortality and resource utilization. The type of vascular access placed for AKI-RRT is an important decision, for which there is a lack of evidence-based guidelines. METHODS: We conducted a prospective cohort study over a 16-month period with 154 patients initiated on AKI-RRT via either a non-tunneled dialysis catheter (NTDC) or a tunneled dialysis catheter (TDC) at an academic hospital. We compared differences in renal replacement delivery and mechanical and infectious outcomes between NTDCs and TDCs. RESULTS: Patients who received TDCs had significantly better RRT delivery, both with continuous venovenous hemofiltration (CVVH) and intermittent hemodialysis (IHD), compared to patients who received NTDCs; these findings were confirmed after multivariable adjustment for AKI-specific disease severity score, history of chronic kidney disease, renal consult team, and AKI cause. In CVVH and IHD, the median venous and arterial blood flow pressures were significantly higher with TDCs compared to NTDCs (p < 0.001). Additionally for CVVH, the median number of interruptions per catheter was higher with NTDCs compared to TDCs (Rate Ratio (RR) 2.7; p < 0.001), and for IHD, a higher median blood flow was seen with TDCs (p < 0.001). There were a significantly higher number of mechanical complications with NTDCs (RR 13.6 p = 0.001). No significant difference was observed between TDCs and NTDCs for positive blood cultures per catheter. CONCLUSIONS: Compared to NTDCs, TDCs for patients with AKI-RRT had improved RRT delivery and fewer mechanical complications. Initial TDC placement for AKI-RRT should be considered when not clinically contraindicated given the potential for improved RRT delivery and outcomes.

Stability of Fibroblast Growth Factor 23 in Human Plasma.

BACKGROUND: Given the important emerging field of fibroblast growth factor 23 (FGF23) biology, there is a growing need for reliable data on FGF23 assay characteristics. We therefore evaluated the effects of different processing and storage conditions on FGF23 stability, as well as the assay precision of FGF23 measurements using 2 commercially available FGF23 ELISA kits. METHODS: We measured plasma concentrations of intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) in duplicate in 12 patients with a wide range of kidney function. We used blinded replicate samples to calculate the interassay CV for both assays. We processed the samples immediately after collection, after 6 h at 22 °C, or after 24 h at 4 °C. We also exposed samples to 0, 1, 2, or 3 freeze-thaw cycles. RESULTS: The interassay CVs for iFGF23 and cFGF23 were 5.2% and 7.2%, respectively. Delayed processing for either 6 h at 22 °C or 24 h at 4 °C had no significant effect on either iFGF23 or cFGF23, although a nonsignificant trend toward decreased iFGF23 concentrations was observed compared with immediate processing (23% relative decline in concentrations under both delayed processing conditions). Three freeze-thaw cycles had no effect on either iFGF23 or cFGF23 concentrations. CONCLUSIONS: FGF23 measurements in human plasma are stable with delayed processing or after undergoing multiple freeze-thaw cycles.