A5001094259- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Medical Imaging Techniques and Applications
- Cancer-related cognitive impairment studies
- Functional Brain Connectivity Studies
- Advanced MRI Techniques and Applications
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Advanced Neuroimaging Techniques and Applications
- Tryptophan and brain disorders
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- MRI in cancer diagnosis
- Williams Syndrome Research
- Radiopharmaceutical Chemistry and Applications
- Neurobiology of Language and Bilingualism
- Peripheral Nerve Disorders
- Lanthanide and Transition Metal Complexes
- Health Systems, Economic Evaluations, Quality of Life
- Frailty in Older Adults
- Orthopedic Surgery and Rehabilitation
Karolinska Institutet
2015-2024
Karolinska University Hospital
2018-2024
Alzheimer’s Disease Neuroimaging Initiative
2023
Union Bank of Switzerland
2023
Aristotle University of Thessaloniki
2022
Stockholm County Council
2017
Svenska Örtmedicinska Institute
2015
General University Hospital of Patras
2012
See Schott and Fox (doi: 10.1093/brain/awv405 ) for a scientific commentary on this article. Alzheimer's disease is multifactorial dementia disorder characterized by early amyloid-β, tau deposition, glial activation neurodegeneration, where the interrelationships between different pathophysiological events are not yet well characterized. In study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic was used to quantify changes in...
Ligands targeting tau for use with positron emission tomography have rapidly been developed during the past several years, enabling in vivo study of pathology patients Alzheimer's disease and related non-Alzheimer's tauopathies. Several candidate compounds developed, showing good vitro characteristics respect to their ability bind deposits; off-target binding, however, has also observed. In this short commentary, we briefly summarize available evidence pertaining binding discuss different...
The aim of this study was to explore the cerebral distribution tau-specific PET tracer [18F]THK5317 (also known as (S)-[18F]THK5117) retention in different stages Alzheimer's disease; and any associations with markers hypometabolism amyloid-beta deposition. Thirty-three individuals were enrolled, including nine patients disease dementia, thirteen mild cognitive impairment (MCI), two non-Alzheimer's healthy controls (five young four elderly). In a multi-tracer design [18F]THK5317, [11C]...
The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay cerebrospinal fluid concentrations amyloid-β42; (ii) centrally measured amyloid-β42 a Meso Scale Discovery assay; (iii) an antibody-independent mass spectrometry-based reference method. Moreover, we examined hypothesis that discordance amyloid biomarker measurements may be...
The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load tau pathology Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled a 17-month follow-up study, including 16 AD (10 had mild cognitive impairment positive amyloid PET scan, that is, prodromal AD, six dementia) two corticobasal syndrome. All underwent scans [18F]THK5317 (tau deposition) [18F]FDG (glucose metabolism) at follow-up,...
Abstract For early detection of Alzheimer’s disease, it is important to find biomarkers with predictive value for disease progression and clinical manifestations, such as cognitive decline. Individuals can now be profiled based on their biomarker status Aβ42 (A) or tau (T) deposition neurodegeneration (N). The aim this study was compare the cerebrospinal fluid (CSF) imaging (PET/MR) in each ATN category assess ability predict longitudinal A subset 282 patients, who had at same time PET...
Several tracers have been designed for tracking the abnormal accumulation of tau pathology in vivo. Recently, concerns raised about sources off-target binding these tracers; inconclusive data propose some to monoamine oxidase B (MAO-B).Molecular docking and dynamics simulations were used estimate affinity free energy several (FDDNP, THK523, THK5105, THK5317, THK5351, T807 [aka AV-1451, flortaucipir], T808, PBB3, RO-948, MK-6240, JNJ-311 PI-2620) MAO-B. These values then compared with those...
The PET tracer <sup>11</sup>C-deuterium-L-deprenyl (<sup>11</sup>C-DED) has been used to visualize activated astrocytes in vivo patients with Alzheimer disease (AD). In this multitracer study, early-phase <sup>11</sup>C-DED and <sup>11</sup>C-Pittsburgh compound B (<sup>11</sup>C-PiB) (eDED ePiB, respectively) were compared as surrogate markers of brain perfusion, the extent which binding is influenced by perfusion was investigated. <b>Methods:</b><sup>11</sup>C-DED, <sup>11</sup>C-PiB,...
Plasma assays for the detection of Alzheimer's disease neuropathological changes are receiving ever increasing interest. The concentration plasma glial fibrillary acidic protein (GFAP) has been suggested as a potential marker astrocytes or recently, amyloid-β burden, although this hypothesis remains unproven. We compared GFAP levels with astrocyte tracer 11C-Deuterium-L-Deprenyl (11C-DED) in multi-modal PET design participants sporadic and Autosomal Dominant disease.Twenty-four individuals...
Because a correlation between tau pathology and the clinical symptoms of Alzheimer disease (AD) has been hypothesized, there is increasing interest in developing PET tracers that bind specifically to protein. The aim this study was evaluate tracer kinetic models for quantitative analysis generation parametric images novel ligand (<i>S</i>)-<sup>18</sup>F-THK5117. <b>Methods:</b> Nine subjects (5 with AD, 4 mild cognitive impairment) received 90-min dynamic...
Assessments of brain glucose metabolism (18F-FDG-PET) and cerebral amyloid burden (11C-PiB-PET) in mild cognitive impairment (MCI) have shown highly variable performances when adopted to predict progression dementia due Alzheimer's disease (ADD). This study investigates, a clinical setting, the separate combined values 18F-FDG-PET 11C-PiB-PET ADD conversion prediction with optimized data analysis procedures. Respectively, we investigate accuracy an SPM for standardized uptake value ratio...
Abstract Background The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification regional tau deposition and offers the opportunity to monitor progression pathology along with cognitive impairment. In this study, we investigated relationships cerebral ([ 18 F]THK5317-PET) metabolism F]FDG-PET) concomitant function patients probable Alzheimer’s disease (AD). Methods Nine diagnosed AD dementia 11 prodromal (mild impairment,...
For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to region (R 1 ) has been shown serve as a marker brain perfusion, and, due strong coupling between perfusion and metabolism, proxy for glucose metabolism. In present study, 11 prodromal Alzheimer’s disease nine dementia patients underwent [ 18 F]THK5317, carbon-11 Pittsburgh Compound-B ([ C]PIB), 2-deoxy-2-[ F]fluoro-D-glucose F]FDG) assess possible use...
To investigate the impact of amyloid PET with [18F]flutemetamol on diagnosis and treatment management in a cohort patients attending tertiary memory clinic whom, despite extensive cognitive assessment including neuropsychological testing, structural imaging, CSF biomarker analysis some cases [18F]FDG PET, remained unclear.The study population consisted 207 clinical prior to mild impairment (MCI; n = 131), Alzheimer's disease (AD; 41), non-AD (n 10), dementia not otherwise specified (dementia...
The spatial resolution of 18F-fluorodeoxyglucose PET does not allow the specific cellular origin its signal to be determined, but it is commonly accepted that transport and trapping reflects neuronal glucose metabolism. main frameworks for diagnosis Alzheimer's disease suggest hypometabolism measured with a biomarker injury neurodegeneration. There preclinical evidence astrocytes contribute, at least partially, in vivo signal. However, due paucity tracers imaging astrocytic processes,...
Though currently approved for visual assessment only, there is evidence to suggest that quantification of amyloid-β (Aβ) PET images may reduce interreader variability and aid in the monitoring treatment effects clinical trials. Quantification typically involves a regional atlas standard space, requiring be spatially normalized. Different uptake patterns Aβ-positive Aβ-negative subjects, however, make spatial normalization challenging. In this study, we proposed method normalize...
Biological subtypes in Alzheimer's disease, originally identified on neuropathological data, have been translated to vivo biomarkers such as structural magnetic resonance imaging and positron emission tomography, disentangle the heterogeneity within disease. Although there is methodological variability across studies, comparable characteristics of are reported at group level. In this study, we investigated whether group-level similarities translate individual-level agreement subtyping...
Abstract Background The 2017 Alzheimer’s disease (AD) Strategic Biomarker Roadmap (SBR) structured the validation of AD diagnostic biomarkers into 5 phases, systematically assessing analytical validity (Phases 1–2), clinical 3–4), and utility (Phase 5) through primary secondary Aims. This framework allows to map knowledge gaps research priorities, accelerating route towards implementation. Within an initiative aimed assess development tau pathology, we revised this methodology consistently...
Abstract Plasma biomarkers have shown promising performance in research cohorts discriminating between different stages of Alzheimer’s disease (AD). Studies clinical populations are necessary to provide insights on the utility plasma before their implementation real-world settings. Here we investigated (glial fibrillary acidic protein (GFAP), tau phosphorylated at 181 and 231 (pTau181, pTau231), amyloid β (Aβ) 42/40 ratio, neurofilament light) 126 patients (age = 65 ± 8) who were admitted...
Background: Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42 ), total-tau (t-tau), and phosphorylated tau (p-tau181p as well with positron emission tomography (PET) usi