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We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

Accurate measurement of Alzheimer's disease (AD) pathology in older adults without significant clinical impairment is critical to assessing intervention strategies aimed at slowing AD-related cognitive decline. The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (POINTER) is a 2-year randomized controlled trial to evaluate the effect of multicomponent risk reduction strategies in older adults (60-79 years) who are cognitively unimpaired but at increased risk for cognitive decline/dementia due to factors such as cardiovascular disease and family history. The POINTER Imaging ancillary study is collecting tau-PET ([18F]MK6240), beta-amyloid (Aβ)-PET ([18F]florbetaben [FBB]) and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at-risk sample. Here 481 participants (70.0±5.0; 66% F) with baseline MK6240, FBB and structural MRI scans were included. PET scans were coregistered to the structural MRI which was used to create FreeSurfer-defined reference regions and target regions of interest (ROIs). We also created off-target signal (OTS) ROIs to examine the magnitude and distribution of MK6240 OTS across the brain as well as relationships between OTS and age, sex, and race. OTS was unimodally distributed, highly correlated across OTS ROIs and related to younger age and sex but not race. Aiming to identify an optimal processing approach for MK6240 that would reduce the influence of OTS, we compared our previously validated MRI-guided standard PET processing and 6 alternative approaches. The alternate approaches included combinations of reference region erosion and meningeal OTS masking before spatial smoothing as well as partial volume correction. To compare processing approaches we examined relationships between target ROIs (entorhinal cortex (ERC), hippocampus or a temporal meta-ROI (MetaROI)) SUVR and age, sex, race, Aβ and a general cognitive status measure, the Modified Telephone Interview for Cognitive Status (TICSm). Overall, the processing approaches performed similarly, and none showed a meaningful improvement over standard processing. Across processing approaches we observed previously reported relationships with MK6240 target ROIs including positive associations with age, an Aβ+> Aβ- effect and negative associations with cognition. In sum, we demonstrated that different methods for minimizing effects of OTS, which is highly correlated across the brain within subject, produced no substantive change in our performance metrics. This is likely because OTS contaminates both reference and target regions and this contamination largely cancels out in SUVR data. Caution should be used when efforts to reduce OTS focus on target or reference regions in isolation as this may exacerbate OTS contamination in SUVR data.

“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18–89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia—Evidence for Amyloid Scanning – Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer's Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of >20/>18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen's k = 0.72 [0.7–0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87–0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R2:0.95, p

We report the first large-scale preparation of fluorinated trannulene C60F15[C(COOMe)3]3(TMCMT) and its application as a photoactive material in organic solar cells. Two types of photovoltaic devices were fabricated: bulk heterojunction cells comprising blends of TMCMTwith a polyfluorene polymer and bilayer cells based on a planar heterojunction of TMCMTwith a perylene diimide. Photoluminescence quenching studies suggested that a photoinduced electron transfer occurs from polyfluorene and perylenediimide to TMCMT, therefore it behaves as photoinduced electron acceptor. Both types of solar cells comprising TMCMTas photoactive material showed clear photovoltaic effects. This proves for the first time the feasibility of the previously anticipated idea of using trannulenes as light-harvesting materials in photovoltaic devices. [ABSTRACT FROM AUTHOR]

We investigated donor−acceptor bilayer heterojunctions formed by deposition of solution-processed pyrrolidinofullerenes bearing chelating pyridyl groups (PyFs) on vacuum-evaporated films of zinc phthalocyanine (ZnPc). It is shown that coordination complexes are formed at the interface between these donor and acceptor components; such association facilitates photoinduced charge separation and results in improved performance of the photovoltaic devices. Thus, the bilayer photovoltaic cells fabricated from different pyrrolidinofullerenes and ZnPc exhibit short circuit current (Isc) densities in the range of 3−5 mA/cm2, open circuit voltages (Voc) of 400−600 mV, and fill factors (FF) of 40−50% that correspond to power conversion efficiencies () of up to 1.5% under 100 mW/cm2simulated AM1.5 illumination. The reference cells based on the nonchelating fullerene derivative 6,6-phenyl-C61butyric acid methyl ester (PCBM) as acceptor component yield lower power conversion efficiencies (0.4−0.6%); the performance of such devices can be increased significantly by mixing PCBM with a small amount (4% w/w) of PyF in the acceptor layer. A novel multicomponent organic solar cell architecture is suggested in order to expand the active layer absorption by formal combination of the solution-processed bulk heterojunction polymer/fullerene cells with evaporated bilayer ZnPc/fullerene devices. For this purpose, a blend of the fullerene derivatives (PCBM and PyF mixed in different ratios) with the polyconjugated polymer poly((2-methoxy-5-(3,7-dimethyloctyloxy)-p-phenylene) vinylene (MDMO−PPV) is spin-coated on the ZnPc film sublimed on an indium tin oxide (ITO) substrate. Evaporation of the top aluminum electrodes yields photovoltaic devices that demonstrate power conversion efficiencies of up to 2% and efficient photocurrent generation in the full range from 350 to 820 nm. [ABSTRACT FROM AUTHOR]