List of publications for week of February 21, 2022
Generation of human induced pluripotent stem cell-derived cerebral organoids for cellular and molecular characterization
(2022) STAR Protocols, 3 (1), art. no. 101173, .
Anastasaki, C., Wilson, A.F., Chen, A.S., Wegscheid, M.L., Gutmann, D.H.
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Human induced pluripotent stem cell (hiPSC)-derived cerebral organoids (COs) can serve as an in vitro model for studying normal and pathologic human brain development. Here, we optimized existing protocols to streamline the generation of forebrain COs from hiPSCs. We employ these COs to define the impact of disease-causing mutations on cell fate, differentiation, maturation, and morphology relevant to neurodevelopmental disorders. Although limited to forebrain CO identity, this schema requires minimal external interference and is amenable to low-throughput biochemical assays. For complete details on the use and execution of this profile, please refer to Anastasaki et al. (2020) and Wegscheid et al. (2021). © 2022 The Author(s)
Author Keywords
Cell Biology; Cell culture; Developmental biology; Health Sciences; Neuroscience; Organoids; Stem Cells
Funding details
National Cancer InstituteNCIR50-CA233164-01
National Institute of Neurological Disorders and StrokeNINDSR35-NS097211-01
National Institute of Biomedical Imaging and BioengineeringNIBIBT32-EB028092
Document Type: Article
Publication Stage: Final
Source: Scopus
Intracranial internal carotid artery calcification is not predictive of future cognitive decline
(2022) Alzheimer’s Research & Therapy, 14 (1), p. 32.
Rahmani, F.a b , Nguyen, M.a b , Chen, C.D.a b , McKay, N.a b , Dincer, A.a b , Joseph-Mathurin, N.a b , Chen, G.a b , Liu, J.c d , Orlowski, H.L.P.a , Morris, J.C.b c , Benzinger, T.L.S.a b
a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, 510 South Kingshighway Boulevard, Campus Box 8131, St. Louis, MO, 63110, USA
b Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC), Washington University, St. Louis, MO, USA
c Department of Neurology, Washington University in Saint Louis, St. Louis, MO, USA
d Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine (WUSM), St. Louis, MO, USA
Abstract
BACKGROUND: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. METHODS: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. RESULTS: Baseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. CONCLUSIONS: In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease. © 2022. The Author(s).
Author Keywords
11C-Pittsburgh compound B; Calcification; Centiloid; Clinical Dementia Rating; Internal carotid artery; Mini-Mental State Exam; PiB; White matter hyperintensities
Document Type: Article
Publication Stage: Final
Source: Scopus
Deep residual inception encoder-decoder network for amyloid PET harmonization
(2022) Alzheimer’s and Dementia, .
Shah, J.a b , Gao, F.a b , Li, B.a b , Ghisays, V.c , Luo, J.c , Chen, Y.c , Lee, W.c , Zhou, Y.d , Benzinger, T.L.S.e , Reiman, E.M.c , Chen, K.c , Su, Y.a b c , Wu, T.a b
a ASU-Mayo Center for Innovative Imaging, Arizona State University, 699 S. Mill Ave., Tempe, AZ 85287, United States
b School of Computing and Augmented Intelligence, Arizona State University, 699 S. Mill Ave., Tempe, AZ 85287, United States
c Banner Alzheimer’s Institute, 901 E. Willetta Street, Phoenix, AZ 85006, United States
d Department of Radiology, Mayo Clinic at Arizona, 5777 E Mayo Blvd, Phoenix, AZ 85054, United States
e Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 510 South Kingshighway Boulevard, St. Louis, MO 63110, United States
Abstract
Introduction: Multiple positron emission tomography (PET) tracers are available for amyloid imaging, posing a significant challenge to consensus interpretation and quantitative analysis. We accordingly developed and validated a deep learning model as a harmonization strategy. Method: A Residual Inception Encoder-Decoder Neural Network was developed to harmonize images between amyloid PET image pairs made with Pittsburgh Compound-B and florbetapir tracers. The model was trained using a dataset with 92 subjects with 10-fold cross validation and its generalizability was further examined using an independent external dataset of 46 subjects. Results: Significantly stronger between-tracer correlations (P <.001) were observed after harmonization for both global amyloid burden indices and voxel-wise measurements in the training cohort and the external testing cohort. Discussion: We proposed and validated a novel encoder-decoder based deep model to harmonize amyloid PET imaging data from different tracers. Further investigation is ongoing to improve the model and apply to additional tracers. © 2022 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association
Author Keywords
Alzheimer’s disease; amyloid PET; Centiloid
Funding details
R01AG055444, R01AG058468, R21AG065942, R42AG053149, U19AG024904
National Institutes of HealthNIHP01 AG003991, P01 AG026276, P30 NS098577, P30AG019610, P50 AG005681, R01 AG043434, R01 EB009352, R01AG031581, R01AG069453, UL1 TR000448
Office of Naval ResearchONR
U.S. Department of Homeland SecurityDHSOT2OD026549, P01AG052350, R01AG054671, U01AG016976, U01NS093334, U54MD000507
Alzheimer’s AssociationAAAARG17532945
Flinn Foundation
Novartis
Roche
BrightFocus Foundation
Arizona Department of Health ServicesADHSCTR040636
University of OklahomaOU
Beijing Normal UniversityBNU
NOMIS Stiftung
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Cerebral oxygen metabolic stress is increased in children with sickle cell anemia compared to anemic controls
(2022) American Journal of Hematology, .
Fields, M.E.a b , Mirro, A.E.a , Binkley, M.M.b , Guilliams, K.P.a b c , Lewis, J.B.b , Fellah, S.b , Chen, Y.b , Hulbert, M.L.a , An, H.c , Ford, A.L.b c , Lee, J.-M.b c d
a Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Patients with sickle cell anemia (SCA) experience cerebral metabolic stress with an increase in oxygen extraction fraction (OEF) to compensate for reduced oxygen carrying capacity due to anemia. It remains unclear if anemia alone drives this metabolic stress. Using MRI, we collected voxel-wise OEF measurements to test our hypothesis that OEF would be elevated in anemic controls without SCA (AC) compared to healthy controls (HC), but OEF would be even higher in SCA compared to AC. Brain MRIs (N = 159) were obtained in 120 participants (34 HC, 27 AC, 59 SCA). While hemoglobin was lower in AC versus HC (p < 0.001), hemoglobin was not different between AC and SCA cohorts (p = 0.459). Whole brain OEF was higher in AC compared to HC (p < 0.001), but lower compared to SCA (p = 0.001). Whole brain OEF remained significantly higher in SCA compared to HC (p = 0.001) while there was no longer a difference between AC versus HC (p = 0.935) in a multivariate model controlling for age and hemoglobin. OEF peaked within the border zone regions of the brain in both SCA and AC cohorts, but the volume of white matter with regionally elevated OEF in AC was smaller (1.8%) than SCA (58.0%). While infarcts colocalized within regions of elevated OEF, more SCA participants had infarcts than AC (p < 0.001). We conclude that children with SCA experience elevated OEF compared to AC and HC after controlling for the impact of anemia, suggesting that there are other pathophysiologic factors besides anemia contributing to cerebral metabolic stress in children with SCA. © 2022 Wiley Periodicals LLC.
Funding details
National Institutes of HealthNIH
National Heart, Lung, and Blood InstituteNHLBIK23HL136904, R01HL129241, R01HL157188
National Institute of Neurological Disorders and StrokeNINDSK23NS099472, U24NS107230
Doris Duke Charitable FoundationDDCF
American Society of HematologyASH
Foundation for Barnes-Jewish Hospital
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
The global Alzheimer’s Association round robin study on plasma amyloid β methods
(2021) Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring, 13 (1), art. no. e12242, .
Pannee, J.a b , Shaw, L.M.c , Korecka, M.c , Waligorska, T.c , Teunissen, C.E.d , Stoops, E.e , Vanderstichele, H.M.J.f , Mauroo, K.e , Verberk, I.M.W.d , Keshavan, A.g , Pesini, P.h , Sarasa, L.h , Pascual-Lucas, M.h , Fandos, N.h , Allué, J.-A.h , Portelius, E.a b , Andreasson, U.a b , Yoda, R.i , Nakamura, A.j , Kaneko, N.i , Yang, S.-Y.k , Liu, H.-C.k , Palme, S.l , Bittner, T.m , Mawuenyega, K.G.n , Ovod, V.n , Bollinger, J.n , Bateman, R.J.n , Li, Y.n , Dage, J.L.o , Stomrud, E.p q , Hansson, O.p q , Schott, J.M.g , Blennow, K.a b , Zetterberg, H.a b r s
a Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
b Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden
c Perelman School of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
d Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
e ADx NeuroSciences, Ghent, Belgium
f Biomarkable, Ghent, Belgium
g Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom
h Araclon Biotech, Zaragoza, Spain
i Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, Kyoto, Japan
j Department of Biomarker Research, National Center for Geriatrics and Gerontology, Aichi, Obu, Japan
k MagQu Co., Ltd., New Taipei City, Taiwan
l Roche Diagnostics GmbH, Penzberg, Germany
m F. Hoffmann-La Roche Ltd, Basel, Switzerland
n Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
o Eli Lilly and Company, Indianapolis, IN, United States
p Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden
q Memory Clinic, Skåne University Hospital, Malmö, Sweden
r Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom
s UK Dementia Research Institute, London, United Kingdom
Abstract
Introduction: Blood-based assays to measure brain amyloid beta (Aβ) deposition are an attractive alternative to the cerebrospinal fluid (CSF)–based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure Aβ and how they compare among centers and assays. Methods: Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass-spectrometric methods were used to measure plasma Aβ concentrations. Results: Correlations were weak for Aβ42 while Aβ40 correlations were stronger. The ratio Aβ42/Aβ40 did not improve the correlations and showed weak correlations. Discussion: The poor correlations for Aβ42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre-analytical sample handling and specificity, and cross-reactivity of different antibodies. Different methods might also measure different pools of plasma Aβ42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study. © 2021 The Authors. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer’s Association
Author Keywords
Alzheimer’s disease; amyloid beta; biomarkers; method comparison; plasma
Document Type: Article
Publication Stage: Final
Source: Scopus