Utility of plasma GFAP as a secondary endpoint for clinical trials in Alzheimer’s disease
Not provided.
Neurosciences & Neurology↗
SEARCH · Search NASA
Results for “neurological disease”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Comparison of Plasma p-tau217 and [ 18 F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia
Not provided.
Neurosciences & Neurology↗
Investigating Neuro-Consequences of Spaceflight Using Drosophila Melanogaster
Research on human acclimation to spaceflight, including the recent NASA's Twin Study, reports complex effects of the spaceflight environment on health, with both acute and prolonged changes in multiple tissues. Spaceflight includes multiple factors such as microgravity, ionizing radiation, physiological stress, and disrupted circadian rhythms, that have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes on the nervous system. With 75% disease gene orthology to humans, short generation time, large sample size and ease of genetic, neuronal and behavioral studies, Drosophila is an excellent model to study nervous system dysfunction. Here, we present results from MVP-Fly-01 spaceflight mission that was launched on SpaceX CRS-14. The MVP hardware (developed by Techshot) used in this mission enabled us to have an in-flight 1g centrifuge, to distinguish the changes resulting from gravity versus those induced by other environmental factors associated with spaceflight. We observe behavioral impairments (p<0.001) and synaptic deficits, including decreased synaptic connections (p<0.05), in 3rd instar larvae which were developed in space. Furthermore, space-grown microgravity adults show a decrease in neuronal (p<0.05) and dendritic field (p<0.01) in adult brains coupled with an increased number of apoptotic cells (p<0.001) compared to in-flight 1g controls, suggesting increased neuronal loss under spaceflight conditions. In summary, we observe that altered gravity leads to gross neurological deficits. To better understand the long-term effects of spaceflight on the nervous system, longitudinal and multigenerational changes were also identified. This study will help elucidate the different approaches to prevent nervous system dysfunction in astronauts during spaceflight, while also contributing to a better understanding of the pathways that are related to some CNS disorders on Earth.
Iyer, Janani↗
Mitigation Strategies for Acute Radiation Exposure during Space Flight
While there are many potential risks in a Moon or Mars mission, one of the most important and unpredictable is that of crew radiation exposure. The two forms of radiation that impact a mission far from the protective environment of low-earth orbit, are solar particle events (SPE) and galactic cosmic radiation (GCR). The effects of GCR occur as a long-term cumulative dose that results increased longer-term medical risks such as malignancy and neurological degeneration. Unfortunately, relatively little has been published on the medical management of an acute SPE that could potentially endanger the mission and harm the crew. Reanalysis of the largest SPE in August 1972 revealed that the dose rate was significantly higher than previously stated in the literature. The peak dose rate was 9 cGy h(sup -1) which exceeds the low-dose-rate criteria for 25 hrs (National Council on Radiation Protection) and 16 hrs (United Nations Scientific Committee on the Effects of Atomic Radiation). The bone marrow dose accumulated was 0.8 Gy, which exceeded the 25 and 16 hour criteria and would pose a serious medical risk. Current spacesuits would not provide shielding from the damaging effects for an SPE as large as the 1972 event, as increased shielding from 1-5 gm/cm(sup 2) would do little to shield the bone marrow from exposure. Medical management options for an acute radiation event are discussed based on recommendations from the Department of Homeland Security, Centers for Disease Control and evidence-based scientific literature. The discussion will also consider how to define acute exposure radiation safety limits with respect to exploration-class missions, and to determine the level of care necessary for a crew that may be exposed to an SPE similar to August 1972.
Hamilton, Douglas R.↗
Mitigation Strategies for Acute Radiation Exposure during Space Flight
While there are many potential risks in a Moon or Mars mission, one of the most important and unpredictable is that of crew radiation exposure. The two forms of radiation that impact a mission far from the protective environment of low-earth orbit, are solar particle events (SPE) and galactic cosmic radiation (GCR). The effects of GCR occur as a long-term cumulative dose that results increased longer-term medical risks such as malignancy and neurological degeneration. Unfortunately, relatively little has been published on the medical management of an acute SPE that could potentially endanger the mission and harm the crew. Reanalysis of the largest SPE in August 1972 revealed that the dose rate was significantly higher than previously stated in the literature. The peak dose rate was 9 cGy h(sup -1) which exceeds the low dose-rate criteria for 25 hrs (National Council on Radiation Protection) and 16 hrs (United Nations Scientific Committee on the Effects of Atomic Radiation). The bone marrow dose accumulated was 0.8 Gy, which exceeded the 25 and 16 hour criteria and would pose a serious medical risk. Current spacesuits would not provide shielding from the damaging effects for an SPE as large as the 1972 event, as increased shielding from 1-5 grams per square centimeters would do little to shield the bone marrow from exposure. Medical management options for an acute radiation event are discussed based on recommendations from the Department of Homeland Security, Centers for Disease Control and evidence-based scientific literature. The discussion will also consider how to define acute exposure radiation safety limits with respect to exploration-class missions, and to determine the level of care necessary for a crew that may be exposed to an SPE similar to August 1972.
Hamilton, Douglas R.↗
Preliminary Evaluations of [ 11 C]Verubulin: Implications for Microtubule Imaging With PET
[ 11 C]Verubulin (a.k.a.[ 11 C]MCP-6827), [ 11 C]HD-800 and [ 11 C]colchicine have been developed for imaging microtubules (MTs) with positron emission tomography (PET). The objective of this work was to conduct an in vivo comparison of [ 11 C]verubulin for MT imaging in mouse and rat brain, as well as an in vitro study with this radiotracer in rodent and human Alzheimer’s Disease tissue. Our preliminary PET imaging studies of [ 11 C]verubulin in rodents revealed contradictory results between mouse and rat brain uptake under pretreatment conditions. In vitro autoradiography with [ 11 C]verubulin showed an unexpected higher uptake in AD patient tissue compared with healthy controls. We also conducted the first comparative in vivo PET imaging study with [ 11 C]verubulin, [ 11 C]HD-800 and [ 11 C]colchicine in a non-human primate. [ 11 C]Verubulin and [ 11 C]HD-800 require pharmacokinetic modeling and quantification studies to understand the role of how these radiotracers bind to MTs before translation to human use.
60 APPLIED LIFE SCIENCES↗
Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease
The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.
Non-NASA Center↗
Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer’s disease spectrum
Abstract Plasma phosphorylated tau (p-tau) biomarkers open unprecedented opportunities for identifying carriers of Alzheimer’s disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment. To address this question, we included 103 cognitively unimpaired elderly and 40 cognitively impaired, amyloid-β-positive individuals from the TRIAD cohort, in addition to 336 cognitively unimpaired and 216 cognitively impaired, amyloid-β-positive older adults from the BioFINDER-2 cohort. Participants had tau PET scans, amyloid PET scans or amyloid CSF, p-tau217, p-tau181 and p-tau231 blood measures, structural T1-MRI and cognitive assessments. In this cross-sectional study, we used regression models and correlation analyses to assess the relationship between plasma biomarkers and cognitive scores. Furthermore, we applied receiver operating characteristic curves to assess cognitive impairment across plasma biomarkers. Finally, we categorized participants into amyloid (A), p-tau (T1) and tau PET (T2) positive (+) or negative (−) profiles and ran non-parametric comparisons to assess differences across cognitive domains. We found that plasma p-tau217 was more associated with cognitive performance than p-tau181 and p-tau231 and that this relationship was particularly strong for memory scores (TRIAD: βp-tau217 = −0.53, βp-tau181 = −0.35 and βp-tau231 = −0.24; BioFINDER-2: βp-tau217 = −0.52, βp-tau181 = −0.24 and βp-tau231 = −0.29). Associations in amyloid-β-positive participants resembled these results, but other cognitive scores also showed strong associations in cognitively impaired individuals. Moreover, plasma p-tau217 outperformed plasma p-tau181 and plasma p-tau231 in identifying memory impairment (area under the curve values for TRIAD: p-tau217 = 0.86, p-tau181 = 0.77 and p-tau231 = 0.75; and for BioFINDER-2: p-tau217 = 0.86, p-tau181 = 0.76 and p-tau231 = 0.81) and in identifying executive function impairment only in the BioFINDER-2 cohort (p-tau217 = 0.82, p-tau181 = 0.76 and p-tau231 = 0.76). Lastly, we showed that subtle memory deficits were present in A+T1+T2− participants for plasma p-tau217 (P = 0.007) and plasma p-tau181 (P = 0.01) in the TRIAD cohort and for all biomarkers across cognitive domains in A+T1+T2− and A+T1+T2− individuals (P < 0.001 in all) in the BioFINDER-2 cohort. The A+T1+T2− individuals showed cognitive deficits in both cohorts (P < 0.001 in all). Together, our results suggest that plasma p-tau217 stands out as a biomarker capable of identifying memory deficits attributable to Alzheimer’s disease and that memory impairment certainly occurs in amyloid-β- and plasma p-tau-positive individuals who have no significant amounts of tau in the neocortex.
Neurosciences & Neurology↗
Misclassification of causes of death among a small all-autopsied group of former nuclear workers: Death certificates vs. autopsy reports
The U.S. Transuranium and Uranium Registries performs autopsies on each of its deceased Registrants as a part of its mission to follow up occupationally-exposed individuals. This provides a unique opportunity to explore death certificate misclassification errors, and the factors that influence them, among this small population of former nuclear workers. Underlying causes of death from death certificates and autopsy reports were coded using the 10 th revision of the International Classification of Diseases (ICD-10). These codes were then used to quantify misclassification rates among 268 individuals for whom both full autopsy reports and death certificates with legible underlying causes of death were available. When underlying causes of death were compared between death certificates and autopsy reports, death certificates correctly identified the underlying cause of death’s ICD-10 disease chapter in 74.6% of cases. The remaining 25.4% of misclassified cases resulted in over-classification rates that ranged from 1.2% for external causes of mortality to 12.2% for circulatory disease, and under-classification rates that ranged from 7.7% for external causes of mortality to 47.4% for respiratory disease. Neoplasms had generally lower misclassification rates with 4.3% over-classification and 13.3% under-classification. A logistic regression revealed that the odds of a match were 2.8 times higher when clinical history was mentioned on the autopsy report than when it was not. Similarly, the odds of a match were 3.4 times higher when death certificates were completed using autopsy findings than when autopsy findings were not used. This analysis excluded cases where it could not be determined if autopsy findings were used to complete death certificates. The findings of this study are useful to investigate the impact of death certificate misclassification errors on radiation risk estimates and, therefore, improve the reliability of epidemiological studies.
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
Metacognition, cortical thickness, and tauopathy in aging
We investigated self-rating of cognitive task performance (self-appraisal) and the difference between self-rating and actual task performance (appraisal discrepancy) in cognitively healthy older adults and their relationship with cortical thickness and Alzheimer's disease (AD) biomarkers, amyloid and tau. All participants (N = 151) underwent neuropsychological testing and 1.5T structural magnetic resonance imaging. A subset (N = 66) received amyloid-PET with [11C] PiB and tau-PET with [18F] Flortaucipir. We found that worse performers had lower self-appraisal ratings, but still overestimated their performance, consistent with the Dunning-Kruger effect. Self-appraisal rating and appraisal discrepancy revealed distinct relationships with cortical thickness and AD pathology. Greater appraisal discrepancy, indicating overestimation, was related to thinning of inferior-lateral temporal, fusiform, and rostral anterior cingulate cortices. Lower self-appraisal was associated with higher entorhinal and inferior temporal tau. These results suggest that overestimation could implicate structural atrophy beyond AD pathology, while lower self-appraisal could indicate early behavioral alteration due to AD pathology, supporting the notion of subjective cognitive decline prior to objective deficits.
59 BASIC BIOLOGICAL SCIENCES↗
Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis
Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.
59 BASIC BIOLOGICAL SCIENCES↗
MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches
A review of recent animal models of amyotrophic lateral sclerosis showed a large number of miRNAs had altered levels of expression in the brain and spinal cord, motor neurons of spinal cord and brainstem, and hypoglossal, facial, and red motor nuclei and were mostly upregulated. Among the miRNAs found to be upregulated in two of the studies were miR-21, miR-155, miR-125b, miR-146a, miR-124, miR-9, and miR-19b, while those downregulated in two of the studies included miR-146a, miR-29, miR-9, and miR-125b. A change of direction in miRNA expression occurred in some tissues when compared (e.g., miR-29b-3p in cerebellum and spinal cord of wobbler mice at 40 days), or at different disease stages (e.g., miR-200a in spinal cord of SOD1(G93A) mice at 95 days vs. 108 and 112 days). In the animal models, suppression of miR-129-5p resulted in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and tended to improve motor neuron survival in the SOD1(G93A) mouse model. Suppression of miR-155 was also associated with increased lifespan, while lowering of miR-29a tended to improve lifespan in males and increase muscle strength in SOD1(G93A) mice. Overexpression of members of miR-17~92 cluster improved motor neuron survival in SOD1(G93A) mice. Treatment with an artificial miRNA designed to target hSOD1 increased lifespan and improved muscle strength in SOD1(G93A) animals. Further studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific miRNAs whose suppression or directed against hSOD1 results in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and improved motor neuron survival in SOD1(G93A) animals.
59 BASIC BIOLOGICAL SCIENCES↗
Connectivity, Pathology, and ApoE4 Interactions Predict Longitudinal Tau Spatial Progression and Memory
ABSTRACT Tau pathology spread into neocortex indicates a transition from healthy aging to Alzheimer's disease (AD). Connectivity between tau epicenters and later accumulating regions of cortex has been proposed as a mechanism of tau spread, but how this relationship changes with greater AD pathology burden or genotype is not understood. We investigated tau accumulation in two key regions, precuneus and inferior temporal cortex, using resting state functional connectivity (rsFC) and longitudinal PET imaging from a multicohort sample of cognitively unimpaired older adults. We examined how baseline tau PET, Aβ PET, and ApoE4 genotype status interact with rsFC between hippocampus and these downstream regions to predict rate of tau accumulation in neocortex. We found that the 3‐way interaction between connectivity, baseline tau, and baseline Aβ or ApoE4 status was associated with neocortical tau accumulation in precuneus and inferior temporal cortex. In addition, baseline tau, Aβ, and ApoE4 status also moderated the association between connectivity and rate of memory decline. Together, these results suggest that the extent and distribution of future tau accumulation may be predicted by the interaction of baseline connectivity, AD pathology, and genetic risk.
Neurosciences & Neurology↗
The cholesterol transporter NPC1 is essential for epigenetic regulation and maturation of oligodendrocyte lineage cells
The intracellular cholesterol transporter NPC1 functions in late endosomes and lysosomes to efflux unesterified cholesterol, and its deficiency causes Niemann–Pick disease Type C, an autosomal recessive lysosomal disorder characterized by progressive neurodegeneration and early death. Here, we use single-nucleus RNA-seq on the forebrain of Npc1 –/– mice at P16 to identify cell types and pathways affected early in pathogenesis. Our analysis uncovers significant transcriptional changes in the oligodendrocyte lineage during developmental myelination, accompanied by diminished maturation of myelinating oligodendrocytes. We identify upregulation of genes associated with neurogenesis and synapse formation in Npc1 –/– oligodendrocyte lineage cells, reflecting diminished gene silencing by H3K27me3. Npc1 –/ – oligodendrocyte progenitor cells reproduce impaired maturation in vitro, and this phenotype is rescued by treatment with GSK-J4, a small molecule inhibitor of H3K27 demethylases. Moreover, mobilizing stored cholesterol in Npc1 –/– mice by a single administration of 2-hydroxypropyl-β-cyclodextrin at P7 rescues myelination, epigenetic marks, and oligodendrocyte gene expression. Our findings highlight an important role for NPC1 in oligodendrocyte lineage maturation and epigenetic regulation, and identify potential targets for therapeutic intervention.
59 BASIC BIOLOGICAL SCIENCES↗
Cognitive aging outcomes are related to both tau pathology and maintenance of cingulate cortex structure
Abstract INTRODUCTION Successful cognitive aging is related to both maintaining brain structure and avoiding Alzheimer's disease (AD) pathology, but how these factors interplay is unclear. METHODS A total of 109 cognitively normal older adults (70+ years old) underwent amyloid beta (Aβ) and tau positron emission tomography (PET) imaging, structural magnetic resonance imaging (MRI), and cognitive testing. Cognitive aging was quantified using the cognitive age gap (CAG), subtracting chronological age from predicted cognitive age. RESULTS Lower CAG (younger cognitive age) was related to slower decline in episodic memory, multi‐domain cognition, and atrophy of the midcingulate cortex (MCC). Lower entorhinal cortical tau was linked to slower decline in episodic memory, multi‐domain cognition, and hippocampal atrophy. DISCUSSION These results suggest that aging outcomes may be influenced by two independent pathways: one associated with tau accumulation, affecting primarily memory and hippocampal atrophy, and another involving tau‐independent structural preservation of the MCC, benefiting multi‐domain cognition over time. Highlights Younger cognitive age (lower cognitive age gap [CAG]) is related to slower cognitive decline. Lower CAG is linked to slower midcingulate cortex (MCC) atrophy. Reduced tau in the entorhinal cortex is related to less hippocampal atrophy and cognitive decline. Structural preservation of the MCC benefits multi‐domain cognition over time. Two independent pathways influence cognitive aging: tau accumulation and MCC preservation.
Neurosciences & Neurology↗
On the nature and evolution of the neural bases of human language
The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.
Review, Tutorial↗
Positron emission tomography harmonization in the Alzheimer's Disease Neuroimaging Initiative: A scalable and rigorous approach to multisite amyloid and tau quantification
Abstract INTRODUCTION A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β‐amyloid (Aβ) and tau PET image data across multiple scanners and tracers. METHODS We developed an analysis pipeline (Berkeley PET Imaging Pipeline, B‐PIP) for ADNI Aβ and tau PET images and applied it to PET data from other multisite studies. Steps include image pre‐processing, refacing, magnetic resonance imaging (MRI)/PET co‐registration, visual quality control (QC), quantification of tracer uptake, and standardization of Aβ and tau standardized uptake value ratios (SUVrs) across tracers. RESULTS Measurements from 10,105 cross‐sectional and longitudinal Aβ and tau PET scans acquired in several studies between 2010 and 2024 can be processed, harmonized, and directly merged across tracers and cohorts. DISCUSSION The B‐PIP developed in ADNI is a scalable image harmonization approach used in several observational studies and clinical trials that facilitates rigorous Aβ and tau PET quantification and data sharing. Highlights Quantitative results from ADNI Aβ and tau PET data are generated using a rigorous, scalable image processing pipeline This pipeline has been applied to PET data from several other large, multisite studies and trials Quantitative outcomes are harmonizable across studies and are shared with the scientific community
Neurosciences & Neurology↗
Calibration of multisite raters for prospective visual reads of amyloid PET scans
Abstract INTRODUCTION In multicenter Alzheimer's disease studies, amyloid positron emission tomography (PET) visual reads are typically performed centrally by a few experts. Incorporating a broader reader network enhances scalability and generalizability. METHODS Ten neuroimaging experts from eight Alzheimer's Disease Research Centers (ADRCs) visually read 180 amyloid PET scans (30 scans and 15 duplicate scans for each of four tracers, imaged across a wide variety of scanners), using preferred reading software without anatomical imaging or quantitation. Scans were classified as elevated or non‐elevated per tracer‐specific criteria. Inter‐ and intra‐rater agreement was assessed. RESULTS Inter‐rater agreement was substantial (Fleiss’κ = 0.78), with full consensus on 69% of scans. Inter‐rater reliability was substantial to perfect across tracers (Fleiss’κ = 0.70–0.87). Intra‐rater agreement was substantial to perfect (Cohen'sκ = 0.79‐1). Scans with intermediate (10–40 Centiloid) quantitation had lower reader agreement. DISCUSSION A multicenter expert network achieved substantial agreement classifying amyloid PET scans. These scans provide a standard for reader training and reliability assurance in future studies. Highlights Calibration methods ensure reliable amyloid positron emission tomography (PET) visual reads across multiple raters. Substantial agreement is possible across readers using their preferred tools. Agreement is also substantial regardless of the amyloid PET tracer used. Scans with intermediate (10–40 Centiloid) quantitation have lower reader agreement. The calibration set will become a training tool for amyloid PET visual read studies.
Neurosciences & Neurology↗