
Konstantinos ChiotisKarolinska Institutet | KI · Center for Alzheimer research
Konstantinos Chiotis
MD, PhD
About
90
Publications
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Publications
Publications (90)
Background
Although ß‐amyloid and tau PET positivity (A+T+) has been related to neurodegeneration and cognitive decline in Alzheimer’s disease (AD), the driving force of neurodegeneration in discordant AT cases remains controversial. We investigated the impact of AT status on longitudinal rates of cortical atrophy and cognitive decline.
Method
A s...
Background
Detecting early stages of Alzheimer's disease (AD) remains a crucial yet complex challenge. While recent interest has surged in detecting biomarkers linked with the disease preclinical phase, a comprehensive understanding of the concomitant peripheral biological pathways before the potential disease onset is necessary. We aim to explore...
Background
The in vivo amyloid‐β (A) and tau (T) biomarkers have been validated against the respective neuropathological burden of amyloid‐β plaques and neurofibrillary tangles. We aimed to assess the impact of mixed pathologies on the interpretation of AT biomarker system.
Method
A subset of 71 ADNI participants with available neuropathological d...
Background
Plasma biomarkers are on the verge of being introduced as screening tools for detecting Alzheimer's disease (AD). Yet, previous studies yielded contradictory results regarding the extent to which distinct plasma biomarkers reflect the key pathological changes associated with AD. This study aims to investigate the specific relationship be...
Background
Studies on plasma biomarkers have shown promising results for Alzheimer’s disease(AD) neuropathology in a research setting, but their associations to neuropsychological(NP) tests have not been extensively studied in clinical cohorts. The main aim was to investigate associations between NP, plasma biomarkers and amyloid accumulation in th...
Background
[¹⁸F]FDG PET is essential since it allows us to differentiate between different dementia disorders/types, revealing distinct neurodegenerative patterns in those predisposed to the condition. Individuals with Autosomal Dominant Alzheimer's Disease (ADAD) have a predictable age of onset, enabling the study of cognitive and pathological cha...
Background
Detecting early stages of Alzheimer's disease (AD) remains a crucial yet complex challenge. While recent interest has surged in detecting biomarkers linked with the disease preclinical phase, a comprehensive understanding of the concomitant peripheral biological pathways before the potential disease onset is necessary. We aim to explore...
Background
Although β‐amyloid and tau PET positivity (A+T+) has been related to neurodegeneration and cognitive decline in Alzheimer’s disease (AD), the driving force of neurodegeneration in discordant AT cases remains controversial. We investigated the impact of AT status on longitudinal rates of cortical atrophy and cognitive decline.
Method
A s...
amyloid (Aβ) pathology is not always coupled with Alzheimer’s disease (AD) relevant cognitive decline. We assessed the accuracy of tau PET to identify Aβ(+) individuals who show prospective disease progression. 396 cognitively unimpaired and impaired individuals with baseline Aβ and tau PET and a follow-up of ≥ 2 years were selected from the Alzhei...
The recent progress in the development of in vivo biomarkers is rapidly changing how neurodegenerative diseases are conceptualized and diagnosed and how clinical trials are designed today. Alzheimer’s disease (AD) – the most common neurodegenerative disorder – is characterized by a complex neuropathology involving the deposition of extracellular am...
Background
Previous studies yielded contradictory findings regarding the association of plasma biomarkers with established biomarkers of tau and amyloid (Aβ) pathology. Here, we aim to examine the relationship between Aβ‐PET and CSF pTau with plasma biomarkers in a cohort of memory clinic patients.
Methods
Plasma GFAP, pTau181, pTau231, and CSF pT...
Background
The Alzheimer’s disease (AD) biomarker field is moving rapidly. Creating a platform where multi‐PET tracer approaches and various fluid biomarkers with discriminative power in the early pathological stages could provide deeper insight into the role of reactive astrogliosis in the AD continuum. Accumulating data indicates that reactive as...
Background
Plasma assays for the detection of Alzheimer’s disease neuropathological changes are receiving ever increasing interest. The concentration of plasma glial fibrillary acidic protein (GFAP) has been suggested as a potential marker of astrocytes or recently, amyloid-β burden, although this hypothesis remains unproven. We compared plasma GFA...
Plasma biomarkers have shown promising performance in research cohorts in discriminating between different stages of Alzheimer's disease (AD). Studies in clinical populations are necessary to provide insights on the clinical utility of plasma biomarkers before their implementation in real-world settings. Here we investigated plasma biomarkers (glia...
Background
Neuroinflammation, which receives ever increasing interest in neurodegenerative diseases, comprises a heterogeneous cascade of events that are thought to be related to the downstream neurodegeneration. The aim of this study was to evaluate the binding of ¹¹ C‐Deuterium‐L‐Deprenyl PET (DED) as a measure of reactive astrocytes in patients...
Background
Synaptic dysfunction plays a key role in cognitive decline during progression of Alzheimer’s disease (AD). Higher levels of several synaptic proteins including the presynaptic protein ß‐synuclein have been measured in cerebrospinal fluid (CSF) of individuals with AD. Recently a quantitative assay using mass spectrometry allowed detection...
Background
We have proposed astrogliosis as a “first wave” of response to AD pathology with diverging longitudinal changes of reactive astrocytes and amyloid‐β positron emission tomography (PET) retention in pre‐symptomatic autosomal dominant AD (ADAD). It has been suggested that plasma glial fibrillary acidic protein (GFAP) could be a marker of ne...
Reactive astrogliosis is an early event in the continuum of Alzheimer’s disease (AD). Current advances in positron emission tomography (PET) imaging provide ways of assessing reactive astrogliosis in the living brain. In this review, we revisit clinical PET imaging and in vitro findings using the multi-tracer approach, and point out that reactive a...
Introduction:
β-synuclein is an emerging blood biomarker to study synaptic degeneration in Alzheimer´s disease (AD), but its relation to amyloid-β (Αβ) pathology is unclear.
Methods:
We investigated the association of plasma β-synuclein levels with [18F] flutemetamol positron emission tomography (PET) in patients with AD dementia (n = 51), mild...
Beta‐amyloid Positron Emission Tomography (PET) efficiently detects beta‐amyloid plaques supporting the presence of a pathophysiological landmark of Alzheimer’s disease (AD) continuum, but lacks specificity regarding the prediction of future cognitive status. The increasing validation of tau PET tracers raises questions about whether a tau PET biom...
Cross-sectional studies have indicated potential for positron emission tomography (PET) in imaging tau pathology in Alzheimer’s disease (AD); however, its prognostic utility remains unproven. In a longitudinal, multi-modal, prognostic study of cognitive decline, 20 patients with a clinical biomarker-based diagnosis in the AD spectrum (mild cognitiv...
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 for Aβ42 (A) or tau (T) deposition and neurodegeneration (N). The aim of this study was to compare the ce...
Background:
In Alzheimer's disease (AD), the abnormal aggregation of hyperphosphorylated tau leads to synaptic dysfunction and neurodegeneration. Recently developed tau PET imaging tracers are candidate biomarkers for diagnosis and staging of AD.
Objective:
We aimed to investigate the discriminative ability of 18F-THK5317 and 18F-flortaucipir tr...
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 validity (Phases 3–4), and clinical utility (Phase 5) through primary and secondary Aims. This framework allows to map knowledge gaps...
Purpose
The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implem...
Background
In the last decade, the research community focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s Disease (AD). In 2017, the Geneva AD Biomarker Roadmap Initiative adapted the framework for the systematic validation of oncological diagnostic biomarkers to AD, with the aim to accelerat...
Background
In the last decade, the research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s Disease (AD). In 2017, the Geneva AD Biomarker Roadmap Initiative adapted the framework for the systematic validation of oncological diagnostic biomarkers (Pepe et al., 2001) to AD, w...
Background
Selective positron emission tomography (PET) tracers to target neurofibrillary tangles of the second generation have indicated to overcome some of the methodological issues observed with the tau‐tracers of the first generation. How these second‐generation tau tracers may be better suitable for clinical practice was assessed in the contex...
Background
Though cerebrospinal fluid (CSF) Aβ42, p‐tau181 and t‐tau have been shown to increase diagnostic accuracy for early Alzheimer’s disease (i.e. AD at the MCI stage), several challenges remain with respect to their routine clinical use. In order to address these and related issues, a multidisciplinary task force was formed (Geneva Biomarker...
Biological subtypes in Alzheimer’s disease, originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within Alzheimer’s disease. Although there is methodological variability across studies,...
Introduction:
The disconnection hypothesis of Alzheimer's disease (AD) is supported by growing neuroimaging and neurophysiological evidence of altered brain functional connectivity in cognitively impaired individuals. Brain functional modalities such as [18F]fluorodeoxyglucose positron-emission tomography ([18F]FDG-PET) and electroencephalography (...
Background: Biological subtypes in Alzheimer's disease (AD), originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within AD. Although there is methodological variability across studies,...
Purpose
To investigate the impact of amyloid PET with [¹⁸F]flutemetamol on diagnosis and treatment management in a cohort of patients attending a tertiary memory clinic in whom, despite extensive cognitive assessment including neuropsychological testing, structural imaging, CSF biomarker analysis and in some cases [¹⁸F]FDG PET, the diagnosis remain...
Purpose
Several tracers have been designed for tracking the abnormal accumulation of tau pathology in vivo. Recently, concerns have been raised about the sources of off-target binding for these tracers; inconclusive data propose binding for some tracers to monoamine oxidase B (MAO-B).
Methods
Molecular docking and dynamics simulations were used to...
Purpose
Studies comparing CSF and PET tau biomarkers have included only commercial CSF assays examining specific phosphorylation sites (e.g. threonine 181, P-tau181p) and mid-domain tau (i.e. total tau, T-tau). Moreover, these studies did not examine CSF tau levels in relation to cerebral glucose metabolism. We thus aimed to examine CSF tau measure...
Purpose
The spatial resolution of ¹⁸F-fluorodeoxyglucose PET does not allow the specific cellular origin of its signal to be determined, but it is commonly accepted that transport and trapping of ¹⁸F-fluorodeoxyglucose reflects neuronal glucose metabolism. The main frameworks for the diagnosis of Alzheimer’s disease suggest that hypometabolism meas...
[¹⁸F]THK5317 is a PET tracer for in-vivo imaging of tau associated with Alzheimer's disease (AD). This work aimed to evaluate optimal timing for standardized uptake value ratio (SUVR) measures with [¹⁸F]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R1) parametric images. Nine AD patients and nine controls underwent 90...
The accumulation of pathological misfolded tau is a feature common to a collective of neurodegenerative disorders known as tauopathies, of which Alzheimer’s disease (AD) is the most common. Related tauopathies include progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), Down’s syndrome (DS), Parkinson’s disease (PD), and dementia with...
Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but la...
Purpose:
Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (11C-THK5351 and 11C-PBB3) in a head-to-head, in vivo, multimodal design.
Methods:
Nine patient...
Though currently approved for visual assessment only, there is evidence to suggest that quantification of amyloid-β (Aβ) PET images may reduce inter-reader variability and aid in the monitoring of treatment effects in clinical trials. Quantification typically involves a regional atlas in standard space, requiring PET images to be spatially normaliz...
Ligands targeting tau for use with positron emission tomography have rapidly been developed during the past several years, enabling the in vivo study of tau pathology in patients with Alzheimer's disease and related non-Alzheimer's disease tauopathies. Several candidate compounds have been developed, showing good in vitro characteristics with respe...
Abnormal aggregation of tau in the brain is a major contributing factor in various neurodegenerative diseases. The role of tau phosphorylation in the pathophysiology of tauopathies remains unclear. Consequently, it is important to be able to accurately and specifically target tau deposits in vivo in the brains of patients. The advances of molecular...
Introduction:
Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single positron emissi...
The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. Ho...
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 to dementia due to Alzheimer's disease (ADD). This study investigates, in a clinical setting, the separate and combined values of 18F-FDG-PET a...
The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PE...
The use of biomarkers has been proposed for diagnosing Alzheimer's disease in recent criteria, but some biomarkers have not been sufficiently investigated to justify their routine clinical use. Here, we evaluate in a literature review the clinical validity of amyloid positron emission tomography (PET) imaging using a structured framework developed...
Background:
The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification of regional tau deposition and offers the opportunity to monitor the progression of tau pathology along with cognitive impairment. In this study, we investigated the relationships of cerebral tau deposition ([(18)F]THK53...
Purpose
The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [18F]THK5317 (also known as (S)-[18F]THK5117) retention in different stages of Alzheimer’s disease; and study any associations with markers of hypometabolism and amyloid-beta deposition.
Methods
Thirty-three individuals were enrolled, including nin...
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 derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso S...
For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to reference region (R1) has been shown to serve as a marker of brain perfusion, and, due to the strong coupling between perfusion and metabolism, as a proxy for glucose metabolism. In the present study, 11 prodrom...