Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aß42/40 ratio to identify presence of brain amyloid.

BACKGROUND: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. METHODS: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aß)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. RESULTS: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. DISCUSSION: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.

Timing of Biomarker Changes in Sporadic Alzheimer's Disease in Estimated Years from Symptom Onset.

OBJECTIVE: A clock relating amyloid positron emission tomography (PET) to time was used to estimate the timing of biomarker changes in sporadic Alzheimer disease (AD). METHODS: Research participants were included who underwent cerebrospinal fluid (CSF) collection within 2 years of amyloid PET. The ages at amyloid onset and AD symptom onset were estimated for each individual. The timing of change for plasma, CSF, imaging, and cognitive measures was calculated by comparing restricted cubic splines of cross-sectional data from the amyloid PET positive and negative groups. RESULTS: The amyloid PET positive sub-cohort (n = 118) had an average age of 70.4 ± 7.4 years (mean ± standard deviation) and 16% were cognitively impaired. The amyloid PET negative sub-cohort (n = 277) included individuals with low levels of amyloid plaque burden at all scans who were cognitively unimpaired at the time of the scans. Biomarker changes were detected 15-19 years before estimated symptom onset for CSF Aß42/Aß40, plasma Aß42/Aß40, CSF pT217/T217, and amyloid PET; 12-14 years before estimated symptom onset for plasma pT217/T217, CSF neurogranin, CSF SNAP-25, CSF sTREM2, plasma GFAP, and plasma NfL; and 7-9 years before estimated symptom onset for CSF pT205/T205, CSF YKL-40, hippocampal volumes, and cognitive measures. INTERPRETATION: The use of an amyloid clock enabled visualization and analysis of biomarker changes as a function of estimated years from symptom onset in sporadic AD. This study demonstrates that estimated years from symptom onset based on an amyloid clock can be used as a continuous staging measure for sporadic AD and aligns with findings in autosomal dominant AD. ANN NEUROL 2024;95:951-965.

Regeneration of per- and polyfluoroalkyl substance-laden granular activated carbon using a solvent based technology.

Per- and polyfluoroalkyl substances (PFAS) are a large class of chemicals widely used for many commercial and industrial applications and have resulted in contamination at sites across globally. Pump-and-treat systems, groundwater extraction, and ex situ treatment using granular activated carbon (GAC) are being implemented, either in full or pilot scale, to treat PFAS-impacted groundwater and drinking water. The only current method of regenerating spent GAC is to reactivate it at temperatures greater than 1000 °C, which requires large amounts of energy and is quite expensive. This research focused on development and demonstration of an effective GAC regeneration technology using a solvent-based method for PFAS-laden GAC used in water treatment. Two different organic solvents (ethanol and isopropyl alcohol) with 0.5% and 1.0% ammonium hydroxide (NH4OH) as a base additive were tested to determine the most effective regenerant solution to remove PFAS from the contaminated GAC. Based on column tests using laboratory-contaminated GAC with perfluorooctanoic acid (PFOA) and perfluorooctanoic sulfonate (PFOS), the solvent-base mix (SBM) of ethanol with 0.5% NH4OH was found to be the optimum performing regenerant solution. The GAC life span assessment showed that solvent-regenerated GAC performed similar to virgin GAC without losing its optimal performance of PFAS sorption. Further, the solvent-regenerated GAC showed optimal performance even after four cycles of solvent regenerations tested using the optimum SBM. Average percent removal in laboratory-contaminated GAC using the optimum SBM was 65% and 93% for PFOS and PFOA, respectively. Four field-spent GAC samples were also regenerated using the optimum SBM. Percent removal from these samples was found to be in range of 55%-68%. The type of GAC used, level of contamination and type of PFAS present, water type and quality, and the presence of co-contaminants may have influenced the removal capacity. Distillation experiments have shown that it is feasible to concentrate the spent solvent prior to disposal, which reduces the amount of PFAS-contaminated solvent waste produced in regeneration cycles.

Stimuli Response of Cationic Polymer Brush Prepared by ATRP: Application in Peptide Fractionation.

Random cationic copolymer brushes composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and N-isopropylacrylamide (NIPAAm) were synthesized using the atom transfer radical polymerization (ATRP) method. The effects of varying the monomer feed ratios (30:70 and 70:30 DMAEMA:NIPAAm) and polymerization times on the film height, morphology and stimuli response to pH of the brush were evaluated. While the polymerization time was found to have little influence on the properties of the brushes, the monomer feed ratios had a great impact. The 70 % DMAEMA polymer brush had similar height as the 30 % DMAEMA brush after 45 min; however, it had a greater response to pH and morphological change compared to the 30 % DMAEMA. The 70 % DMAEMA brush was used to demonstrate an efficient approach to alleviate the ion suppression effect in MALDI analysis of complex mixtures by effectively fractionating a binary mixture of peptides prior to MALDI-MS analysis.

Peptide/protein separation with cationic polymer brush nanosponges for MALDI-MS analysis.

A cationic polymer nanobrush was synthesized, attached to a MALDI target, and used for the fractionation of peptides and proteins based on their pI, prior to analysis by MALDI-MS. The cationic polymer nanobrush was synthesized on a gold substrate by AIBN photoinitiated polymerization, using a 70:30 ratio of 2-aminoethyl methacrylate hydrochloride (AEMA):N-isopropylacrylamide (NIPAAM). This brush showed selectivity for adsorption of acidic peptides and proteins and allowed fractionation of simple two-component mixtures to be completed in less than 10 min. The brush-adsorbed biomolecules were recovered by treating the nanobrush with ammonium hydroxide, which effectively collapsed the brush, thereby releasing the trapped compounds for MALDI MS analysis. These results demonstrate that nanobrush can serve as a convenient platform for rapid fractionation of biomolecules prior to analysis by MALDI-MS.