Agneta Nordberg

Agneta Nordberg
Karolinska Institutet | KI · Department of Neurobiology, Care Sciences and Society - NVS, Translational Alzheimer Neurobiology

MD PHD PROFESSOR

About

840
Publications
76,852
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43,732
Citations
Additional affiliations
January 1992 - present
Karolinska University Hospital
Position
  • Professor ,Senior Consultant

Publications

Publications (840)
Article
Full-text available
AMYPAD Diagnostic and Patient Management Study (DPMS) aims to investigate the clinical utility and cost‐effectiveness of amyloid‐PET in Europe. Here we present participants’ baseline features and discuss the representativeness of the cohort. Participants with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia wer...
Article
Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design. Objective:...
Article
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The homo-pentameric alpha 7 receptor is one of the major types of neuronal nicotinic acetylcholine receptors (α7-nAChRs) related to cognition, memory formation, and attention processing. The mapping of α7-nAChRs by PET pulls a lot of attention to realize the mechanism and development of CNS diseases such as AD, PD, and schizophrenia. Several PET ra...
Article
Astrocytes are highly efficient homeostatic glial cells playing a crucial role in the optimal brain functioning and homeostasis. Astrocytes respond to changes in brain homoeostasis following central nervous system (CNS) injury/diseased state by a specific defense mechanism called reactive astrogliosis. Recent studies have implicated and placed reac...
Article
In 2018, the National Institute of Aging and the Alzheimer Association proposed a purely biological definition of Alzheimer’s disease (AD) relying on biomarkers. While the intended use of the framework was for research purposes, it has engendered debate and challenges regarding its application in everyday clinical practice. We performed a literatur...
Article
In 2018, the National Institute of Aging and the Alzheimer Association proposed a purely biological definition of Alzheimer’s disease (AD) relying on biomarkers. While the intended use of the framework was for research purposes, it has engendered debate and challenges regarding its application in everyday clinical practice. For instance, cognitivel...
Conference Paper
AMYPAD‐DPMS is a European, multicenter, prospective, interventional, randomized controlled study. It aims to assess clinical utility and cost‐effectiveness of amyloid‐PET. It recruited individuals with Subjective Cognitive Decline plus (SCD+), and syndromic diagnosis of Mild Cognitive Impairment (MCI) and dementia. Here, we describe the quantitativ...
Article
The concept of pathophysiologically profiling individuals based on their biomarker status for Aβ42 (A) or tau (T) deposition and neurodegeneration (N) is attracting interest in the Alzheimer’s disease research field. All three processes can be monitored by either cerebrospinal fluid (CSF) sampling or imaging (PET/MRI). We aimed to test the comparab...
Article
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Autosomal-dominant Alzheimer’s disease (ADAD) may be associated with atypical amyloid beta deposits in the brain. In vivo amyloid imaging using 11C-Pittsburgh compound B (PiB) tracer has shown differences in binding between brains from ADAD and sporadic Alzheimer’s disease (sAD) patients. To gain further insight into the various pathological charac...
Article
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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...
Article
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Mismatch between CSF and PET amyloid-β biomarkers occurs in up to ≈20% of preclinical/prodromal Alzheimer's disease individuals. Factors underlying mismatching results remain unclear. In this study we hypothesized that CSF/PET discordance provides unique biological/clinical information. To test this hypothesis, we investigated non-demented and deme...
Article
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With reactive astrogliosis being established as one of the hallmarks of Alzheimer’s disease (AD), there is high interest in developing novel positron emission tomography (PET) tracers to detect early astrocyte reactivity. BU99008, a novel astrocytic PET ligand targeting imidazoline-2 binding sites (I2BS) on astrocytes, might be a suitable candidate...
Article
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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...
Article
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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...
Article
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Alzheimer’s disease and primary tauopathies are characterized by the presence of tau pathology in brain. Several tau positron emission tomography (PET) tracers have been developed and studied in Alzheimer’s disease (AD), but there is still a lack of 4R-tau specific tracers for non-AD tauopathies. We here present the first computational study on the...
Preprint
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INTRODUCTION Different subtypes/patterns have been defined using tau-PET and structural-MRI in Alzheimer’s disease (AD), but the relationship between tau pathology and atrophy remains unclear. Our goals were twofold: (a) investigate the association between baseline tau-PET patterns and longitudinal atrophy in the AD continuum; (b) characterize hete...
Article
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Purpose In 2017, the Geneva Alzheimer’s disease (AD) Biomarker Roadmap initiative adapted the framework of the systematic validation of oncological diagnostic biomarkers to AD biomarkers, with the aim to accelerate their development and implementation in clinical practice. With this work, we assess the maturity of [¹⁸F]flortaucipir PET and define i...
Article
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Purpose In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into th...
Article
Full-text available
Purpose In the last decade, the research community has focused on defining reliable biomarkers for the early detection of Alzheimer’s disease (AD) pathology. In 2017, the Geneva AD Biomarker Roadmap Initiative adapted a framework for the systematic validation of oncological biomarkers to cerebrospinal fluid (CSF) AD biomarkers—encompassing the 42 a...
Article
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Purpose The development of blood biomarkers that reflect Alzheimer’s disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomark...
Article
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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...
Article
Full-text available
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...
Article
Full-text available
Background [¹⁸F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual interpretation as either negative (equating to none or sparse amyloid plaques) or amyloid positive (equating to moderate or frequent plaques). Quantitation is however fundamental to the practice of nu...
Article
Full-text available
Tauopathies are a subclass of neurodegenerative diseases characterized by an accumulation of microtubule binding tau fibrils in brain regions. Diseases such as Alzheimer’s (AD), chronic traumatic encephalopathy (CTE), Pick’s disease (PiD), and corticobasal degeneration (CBD) belong to this subclass. Development of tracers which can visualize and di...
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Objective To perform a systematic review and meta-analysis to determine whether fluid and imaging astrocyte biomarkers are altered in Alzheimer's disease (AD). Methods PubMed and Web of Science databases were searched for articles reporting fluid or imaging astrocyte biomarkers in AD. Pooled effect sizes were determined with mean differences (SMD)...
Article
Background: The effect of regional brain amyloid-β (Aβ) pathology on specific cognitive functions is incompletely known. Objective: The relationship between Aβ and cognitive functions was investigated in this cross-sectional multicenter study of memory clinic patients. Methods: The participants were patients diagnosed with Alzheimer's disease...
Article
In 2018, the US National Institute on Aging and the Alzheimer's Association proposed a purely biological definition of Alzheimer's disease that relies on biomarkers. Although the intended use of this framework was for research purposes, it has engendered debate and challenges regarding its use in everyday clinical practice. For instance, cognitivel...
Article
Full-text available
Purpose: MK6240 is a second-generation tau PET tracer designed to detect the neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). The aim of the study was to characterize 3H-MK6240 in AD and control brain tissue and to compare its binding properties with those of first-generation tau PET tracers. Methods: Saturation b...
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Background: Emerging evidence indicates a central role of gliosis in Alzheimer's disease (AD) pathophysiology. However, the regional distribution and interaction of astrogliosis and microgliosis in association with amyloid-β (Aβ) still remain uncertain. Objective: Here we studied the pathological profiles in autopsy AD brain by using specific im...
Article
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PurposeTo assess the clinical impact and incremental diagnostic value of 18F-fluorodeoxyglucose (FDG-PET) among memory clinic patients with uncertain diagnosis.Methods The study population consisted of 277 patients who, despite extensive baseline cognitive assessment, MRI, and CSF analyses, had an uncertain diagnosis of mild cognitive impairment (M...
Article
The increasing prevalence of dementia worldwide places a high demand on healthcare providers to perform a diagnostic work-up in relatively early stages of the disease, given that the pathologic process usually begins decades before symptoms are evident. Structural imaging is recommended to rule out other disorders and can only provide diagnosis in...
Article
Full-text available
The α7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in a variety of neurodegenerative and neuropsychiatric disorders, such as Alzheimer's disease (AD) and schizophrenia. The progress of these disorders can be studied using positron emission tomography (PET) with radiotracers for α7-nAChR. [¹⁸F]ASEM and [¹⁸F] para-ASEM (also referred to...
Conference Paper
Identification of biological subtypes in Alzheimer’s disease (AD) has become a growing field for understanding the heterogeneity of the disease. Subtypes, originally identified by postmortem markers (Murray et al., 2011), have been translated to utilize in vivo biomarkers such as those based on structural magnetic resonance imaging (sMRI) and posit...
Article
[18F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual interpretation of scans as either negative (equating to none or sparse amyloid plaques in pathology SoT), or amyloid positive (equating to moderate or frequent plaques). Quantitation is however fundamental to th...
Article
Recently, we provided evidence that discordance in CSF vs. PET Aβ‐biomarkers represents a natural phase in the progression of Aβ‐pathology, with either CSF or PET becoming abnormal first (Figure 1). The reasons why CSF‐Aβ42 becomes abnormal first in some subjects, while Aβ‐PET does in others, are unknown. Here, we aimed to investigate biomarker and...
Conference Paper
AMYPAD‐DPMS is the largest European, multicenter, prospective and randomized study assessing clinical utility and cost‐effectiveness of amyloid‐PET in a controlled but realistic clinical setting. In the present abstract we report preliminary results on the baseline features of the first study participants. A total of 900 participants (300 with subj...
Conference Paper
Amyloid‐PET is increasingly used for diagnostic purposes in patients with cognitive impairment due to suspected Alzheimer’s disease. However, cognitively unimpaired individuals are frequently included in research studies involving amyloid‐PET scan. Even if amyloid‐PET is not clinically recommended in these cases, these patients often want to know t...
Article
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 accelerate their dev...
Article
The 2017 Alzheimer’s disease (AD) Biomarker Roadmap structures the validation of AD diagnostic biomarkers into a systematic sequence of 5 Phases, each encompassing primary and secondary aims assessing analytical validity (Phases 1‐2), clinical validity (Phases 3‐4) and clinical utility (Phase 5). This framework allows us to assess current evidence...
Article
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, with the aim...
Article
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 context of the Ge...
Article
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 Roadmap In...
Article
Full-text available
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,...
Article
Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However,...
Article
Full-text available
Introduction Tau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue o...
Article
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 (...
Article
Empirical evidence suggests that a fair proportion of dementia cases are preventable, that some preventive actions can be taken immediately, and others may soon be implemented. Primary prevention may target cognitively normal persons with modifiable risk factors through lifestyle and multiple domain interventions (including general cardiovascular h...
Preprint
Full-text available
INTRODUCTION: Tau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue...
Preprint
Full-text available
INTRODUCTION: Tau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue...
Article
Full-text available
Introduction: Several pharmacoepidemiological studies indicate that proton pump inhibitors (PPIs) significantly increase the risk of dementia. Yet, the underlying mechanism is not known. Here, we report the discovery of an unprecedented mode of action of PPIs that explains how PPIs may increase the risk of dementia. Methods: Advanced in silico d...
Preprint
Full-text available
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,...
Article
Full-text available
Objective To study the macrostructural and microstructural MRI correlates of brain astrocytosis, measured with ¹¹ C-deuterium-L-deprenyl ( ¹¹ C-DED)–PET, in familial autosomal dominant Alzheimer disease (ADAD). Methods The total sample (n = 31) comprised ADAD mutation carriers (n = 10 presymptomatic, 39.2 ± 10.6 years old; n = 3 symptomatic, 55.5...
Article
Abnormal deposition of hyperphosphorylated tau as neurofibrillary tangles (NFTs) is an important pathological hallmark of Alzheimer’s disease (AD) and of other neurodegenerative disorders. A non-invasive positron emission tomography (PET) tracer that quantifies neurofibrillary tangles in vivo can enhance the clinical diagnosis of AD and can also be...
Article
Full-text available
Objective: To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data. Methods: EMBASE, PubMed, and Web of Science databases were consulted until July 2019. Results: Neu...
Article
p>Almost 50 million people worldwide are affected by Alzheimer’s disease (AD), the most common neurodegenerative disorder. Development of disease-modifying therapies would benefit from reliable, non-invasive positron emission tomography (PET) biomarkers for early diagnosis, monitoring of disease progression, and assessment of therapeutic effects. T...
Article
Full-text available
Objective The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods We measured Aβ42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose–positron emission tomogra...
Article
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Alzheimer’s disease (AD) is a progressive disease with early degeneration of the central cholinergic neurons. Currently, three of four AD drugs act by inhibiting the acetylcholine (ACh) degrading enzyme, acetylcholinesterase (AChE). Efficacy of these drugs depends on available amount of ACh, which is biosynthesized by choline acetyltransferase (ChA...
Article
The purpose was to compare longitudinal cognitive changes in APP and PSEN1 gene mutation carriers and noncarriers from four autosomal-dominant Alzheimer's disease (ADAD) families across preclinical and early clinical stages of disease. Carriers (n = 34) with four different mutations (PSEN1M146V, PSEN1H163Y, APPSWE, and APPARC) and noncarriers (n =...
Article
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Background: A fundamental question in Alzheimer’s disease (AD) is whether amyloid-β (Aβ) peptides and their deposition in the brain signify a direct pathological role or they are mere outcome of the disease pathophysiological events affecting neuronal function. It is therefore important to decipher their physiological role in the brain. So far, the...