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Article ; Online: Phenotyping Alzheimer's disease with blood tests.

Blennow, Kaj

2021 Volume 373, Issue 6555, Page(s) 626–628

MeSH term(s)	Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/blood ; Apolipoprotein E4/genetics ; Biomarkers/blood ; Cerebral Amyloid Angiopathy/blood ; Cerebral Amyloid Angiopathy/diagnosis ; Cerebral Amyloid Angiopathy/pathology ; Humans ; Peptide Fragments/blood ; Phenotype ; Phosphorylation ; Positron-Emission Tomography ; tau Proteins/blood
Chemical Substances	Amyloid beta-Peptides ; Apolipoprotein E4 ; Biomarkers ; MAPT protein, human ; Peptide Fragments ; amyloid beta-protein (1-40) ; amyloid beta-protein (1-42) ; tau Proteins
Language	English
Publishing date	2021-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abi5208
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

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Article ; Online: Analytical and clinical validation of Alzheimer's disease blood biomarkers with a focus on plasma p-tau217.

Gonzalez-Ortiz, Fernando / Karikari, Thomas K / Blennow, Kaj

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 4, Page(s) 3114–3115

Abstract: Alzheimer's disease (AD) represents a growing global health challenge, necessitating accurate and reliable diagnostic methodologies for timely intervention and management. Immunoassays, specifically designed to detect biomarkers associated with AD ... ...

Abstract	Alzheimer's disease (AD) represents a growing global health challenge, necessitating accurate and reliable diagnostic methodologies for timely intervention and management. Immunoassays, specifically designed to detect biomarkers associated with AD pathology, have emerged as pivotal tools in diagnostic development. Understanding of the established protocols ensures assay sensitivity, specificity, and reproducibility, thereby enhancing the clinical utility of these diagnostic tools. Here, we explore the considerations in immunoassay development, focusing on phosphorylated tau217 assays. Ultimately, a clear understanding of immunoassay development is paramount in advancing the precision and reliability of AD diagnostics, contributing to early detection, improved patient outcomes, and advancements in therapeutic interventions.
MeSH term(s)	Humans ; Reproducibility of Results ; Alzheimer Disease/diagnosis ; Plasma ; Biomarkers ; tau Proteins ; Amyloid beta-Peptides
Chemical Substances	Biomarkers ; tau Proteins ; Amyloid beta-Peptides
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Letter
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13708
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Zs.A 6316: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 540: Show issues

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Article ; Online: Alzheimer's Disease Biomarker Analysis Using Targeted Mass Spectrometry.

Gobom, Johan / Brinkmalm, Ann / Brinkmalm, Gunnar / Blennow, Kaj / Zetterberg, Henrik

Molecular & cellular proteomics : MCP

2024 Volume 23, Issue 2, Page(s) 100721

Abstract: Alzheimer's disease (AD) is characterized by several neuropathological changes, mainly extracellular amyloid aggregates (plaques), intraneuronal inclusions of phosphorylated tau (tangles), as well as neuronal and synaptic degeneration, accompanied by ... ...

Abstract	Alzheimer's disease (AD) is characterized by several neuropathological changes, mainly extracellular amyloid aggregates (plaques), intraneuronal inclusions of phosphorylated tau (tangles), as well as neuronal and synaptic degeneration, accompanied by tissue reactions to these processes (astrocytosis and microglial activation) that precede neuronal network disturbances in the symptomatic phase of the disease. A number of biomarkers for these brain tissue changes have been developed, mainly using immunoassays. In this review, we discuss how targeted mass spectrometry (TMS) can be used to validate and further characterize classes of biomarkers reflecting different AD pathologies, such as tau- and amyloid-beta pathologies, synaptic dysfunction, lysosomal dysregulation, and axonal damage, and the prospect of using TMS to measure these proteins in clinical research and diagnosis. TMS advantages and disadvantages in relation to immunoassays are discussed, and complementary aspects of the technologies are discussed.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; tau Proteins/metabolism ; Brain/metabolism ; Amyloid beta-Peptides/metabolism ; Biomarkers/metabolism
Chemical Substances	tau Proteins ; Amyloid beta-Peptides ; Biomarkers
Language	English
Publishing date	2024-01-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2075924-1
ISSN	1535-9484 ; 1535-9476
ISSN (online)	1535-9484
ISSN	1535-9476
DOI	10.1016/j.mcpro.2024.100721
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Article: A Review of Fluid Biomarkers for Alzheimer's Disease: Moving from CSF to Blood.

Blennow, Kaj

Neurology and therapy

2017 Volume 6, Issue Suppl 1, Page(s) 15–24

Abstract: A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal ... ...

Abstract	A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal degeneration, tau phosphorylation with tangle formation, and Aβ aggregation with deposition of the peptide into plaques. The core AD CSF biomarkers have been validated clinically in numerous studies, and found to have a very high diagnostic performance to identify AD, both in the dementia and in the mild cognitive impairment stages of the disease. CSF Aβ42 has also been found to show very high concordance with amyloid PET to identify brain amyloid deposition. The synaptic protein neurogranin is a novel candidate CSF biomarker for AD and prodromal AD. High CSF neurogranin predicts future cognitive decline and seems to be more specific for AD than, for example, T-tau. Importantly, technical developments have given ultrasensitive measurement techniques that allow measurement of brain-specific proteins such as tau and neurofilament light (NFL) in blood samples. Both plasma tau and NFL are increased in AD, and a recent study showed that plasma NFL has a diagnostic performance comparable to the core AD CSF biomarkers, and predicted future cognitive decline. Future large longitudinal clinical studies are warranted to determine the potential for plasma tau and NFL to serve as first-in-line screening tools for neurodegeneration in primary care.
Language	English
Publishing date	2017-07-21
Publishing country	New Zealand
Document type	Journal Article ; Review
ISSN	2193-8253
ISSN	2193-8253
DOI	10.1007/s40120-017-0073-9
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Article: Clinical stage and plasma neurofilament concentration in adults with Friedreich ataxia.

Johnsson, Magnus / Zetterberg, Henrik / Blennow, Kaj / Lindberg, Christopher

Heliyon

2023 Volume 10, Issue 1, Page(s) e23347

Abstract: Objectives: Friedreich Ataxia (FRDA) is the most common recessive ataxia disorder. Yet, little is known of the prevalence in Sweden. In the future, there may be effective disease-modifying therapies, and use of clinical rating scales as well as possible ...

Abstract	Objectives: Friedreich Ataxia (FRDA) is the most common recessive ataxia disorder. Yet, little is known of the prevalence in Sweden. In the future, there may be effective disease-modifying therapies, and use of clinical rating scales as well as possible biomarkers in serum or cerebrospinal fluid may be of importance. We evaluated the axonal protein neurofilament light in plasma ( Materials & methods: We searched for all possible genetically confirmed FRDA cases in the Västra Götaland Region (VGR) of Sweden, and investigated each patient clinically and obtained blood sample for analysis of Results: We found eight patients corresponding to 1/170.000 adults in the VGR, and 5 of these participated in the study. Three out of the five FRDA patients displayed a small or moderate increase in the Conclusions: FRDA is less prevalent in our region of Sweden than could be assumed. In concordance with previous studies from other authors, we find that
Language	English
Publishing date	2023-12-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e23347
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Article ; Online: Next-generation proteomics technologies in Alzheimer's disease: from clinical research to routine diagnostics.

Weiner, Sophia / Blennow, Kaj / Zetterberg, Henrik / Gobom, Johan

Expert review of proteomics

2023 Volume 20, Issue 7-9, Page(s) 143–150

Abstract: Introduction: Clinical proteomics studies of Alzheimer's disease (AD) research aim to identify biomarkers useful for clinical research, diagnostics, and improve our understanding of the pathological processes involved in the disease. The rapidly ... ...

Abstract	Introduction: Clinical proteomics studies of Alzheimer's disease (AD) research aim to identify biomarkers useful for clinical research, diagnostics, and improve our understanding of the pathological processes involved in the disease. The rapidly increasing performance of proteomics technologies is likely to have great impact on AD research. Areas covered: We review recent proteomics approaches that have advanced the field of clinical AD research. Specifically, we discuss the application of targeted mass spectrometry (MS), labeling-based and label-free MS-based as well as affinity-based proteomics to AD biomarker development, underpinning their importance with the latest impactful clinical studies. We evaluate how proteomics technologies have been adapted to meet current challenges. Finally, we discuss the limitations and potential of proteomics techniques and whether their scope might extend beyond current research-based applications. Expert opinion: To date, proteomics technologies in the AD field have been largely limited to AD biomarker discovery. The recent development of the first successful disease-modifying treatments of AD will further increase the need for blood biomarkers for early, accurate diagnosis, and CSF biomarkers that reflect specific pathological processes. Proteomics has the potential to meet these requirements and to progress into clinical routine practice, provided that current limitations are overcome.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Proteomics/methods ; Mass Spectrometry/methods ; Biomarkers ; Biomedical Research
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-09-13
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2299100-1
ISSN	1744-8387 ; 1478-9450
ISSN (online)	1744-8387
ISSN	1478-9450
DOI	10.1080/14789450.2023.2255752
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Article ; Online: Blood biomarkers for Alzheimer's disease in clinical practice and trials.

Hansson, Oskar / Blennow, Kaj / Zetterberg, Henrik / Dage, Jeffrey

Nature aging

2023 Volume 3, Issue 5, Page(s) 506–519

Abstract: Blood-based biomarkers hold great promise to revolutionize the diagnostic and prognostic work-up of Alzheimer's disease (AD) in clinical practice. This is very timely, considering the recent development of anti-amyloid-β (Aβ) immunotherapies. Several ... ...

Abstract	Blood-based biomarkers hold great promise to revolutionize the diagnostic and prognostic work-up of Alzheimer's disease (AD) in clinical practice. This is very timely, considering the recent development of anti-amyloid-β (Aβ) immunotherapies. Several assays for measuring phosphorylated tau (p-tau) in plasma exhibit high diagnostic accuracy in distinguishing AD from all other neurodegenerative diseases in patients with cognitive impairment. Prognostic models based on plasma p-tau levels can also predict future development of AD dementia in patients with mild cognitive complaints. The use of such high-performing plasma p-tau assays in the clinical practice of specialist memory clinics would reduce the need for more costly investigations involving cerebrospinal fluid samples or positron emission tomography. Indeed, blood-based biomarkers already facilitate identification of individuals with pre-symptomatic AD in the context of clinical trials. Longitudinal measurements of such biomarkers will also improve the detection of relevant disease-modifying effects of new drugs or lifestyle interventions.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Tomography, X-Ray Computed ; Amyloid beta-Peptides/cerebrospinal fluid ; Cognitive Dysfunction/diagnosis ; Biomarkers
Chemical Substances	Amyloid beta-Peptides ; Biomarkers
Language	English
Publishing date	2023-05-18
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-023-00403-3
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Article ; Online: Moving fluid biomarkers for Alzheimer's disease from research tools to routine clinical diagnostics.

Zetterberg, Henrik / Blennow, Kaj

Molecular neurodegeneration

2021 Volume 16, Issue 1, Page(s) 10

Abstract: Four fluid-based biomarkers have been developed into diagnostic tests for Alzheimer's disease (AD) pathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology; total-tau and phosphorylated tau, markers of AD-related changes ... ...

Abstract	Four fluid-based biomarkers have been developed into diagnostic tests for Alzheimer's disease (AD) pathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology; total-tau and phosphorylated tau, markers of AD-related changes in tau metabolism and secretion; and neurofilament light, a marker of neurodegeneration. When measured in cerebrospinal fluid, these biomarkers can be used in clinical practice to support a diagnosis of mild cognitive impairment or dementia due to AD. Recently, technological breakthroughs have made it possible to measure them in standard blood samples as well. Here, we give an updated account of the current state of the fluid-based AD biomarker research field. We discuss how the new blood tests may be used in research and clinical practice, and what role they may play in relation to more established diagnostic tests, such as CSF biomarkers and amyloid and tau positron emission tomography, to facilitate the effective implementation of future disease-modifying therapies.
MeSH term(s)	Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Cognitive Dysfunction/cerebrospinal fluid ; Cognitive Dysfunction/diagnosis ; Humans ; Peptide Fragments/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments ; tau Proteins
Language	English
Publishing date	2021-02-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1750-1326
ISSN (online)	1750-1326
DOI	10.1186/s13024-021-00430-x
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Article ; Online: Spatial neurolipidomics-MALDI mass spectrometry imaging of lipids in brain pathologies.

Jha, Durga / Blennow, Kaj / Zetterberg, Henrik / Savas, Jeffrey N / Hanrieder, Jörg

Journal of mass spectrometry : JMS

2024 Volume 59, Issue 3, Page(s) e5008

Abstract: Given the complexity of nervous tissues, understanding neurochemical pathophysiology puts high demands on bioanalytical techniques with respect to specificity and sensitivity. Mass spectrometry imaging (MSI) has evolved to become an important, ... ...

Abstract	Given the complexity of nervous tissues, understanding neurochemical pathophysiology puts high demands on bioanalytical techniques with respect to specificity and sensitivity. Mass spectrometry imaging (MSI) has evolved to become an important, biochemical imaging technology for spatial biology in biological and translational research. The technique facilitates comprehensive, sensitive elucidation of the spatial distribution patterns of drugs, lipids, peptides, and small proteins in situ. Matrix-assisted laser desorption ionization (MALDI)-based MSI is the dominating modality due to its broad applicability and fair compromise of selectivity, sensitivity price, throughput, and ease of use. This is particularly relevant for the analysis of spatial lipid patterns, where no other comparable spatial profiling tools are available. Understanding spatial lipid biology in nervous tissue is therefore a key and emerging application area of MSI research. The aim of this review is to give a concise guide through the MSI workflow for lipid imaging in central nervous system (CNS) tissues and essential parameters to consider while developing and optimizing MSI assays. Further, this review provides a broad overview of key developments and applications of MALDI MSI-based spatial neurolipidomics to map lipid dynamics in neuronal structures, ultimately contributing to a better understanding of neurodegenerative disease pathology.
MeSH term(s)	Humans ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Neurodegenerative Diseases/diagnostic imaging ; Workflow ; Brain/diagnostic imaging ; Lipids
Chemical Substances	Lipids
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1221763-3
ISSN	1096-9888 ; 1076-5174
ISSN (online)	1096-9888
ISSN	1076-5174
DOI	10.1002/jms.5008
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Zs.A 4254: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 220: Show issues

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Article ; Online: Plasma concentrations of glial fibrillary acidic protein, neurofilament light, and tau in Alexander disease.

Ashton, Nicholas J / Di Molfetta, Guglielmo / Tan, Kübra / Blennow, Kaj / Zetterberg, Henrik / Messing, Albee

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2024

Abstract: Introduction: Alexander disease (AxD) is a rare leukodystrophy caused by dominant gain-of-function mutations in the gene encoding the astrocyte intermediate filament, glial fibrillary acidic protein (GFAP). However, there is an urgent need for ... ...

Abstract	Introduction: Alexander disease (AxD) is a rare leukodystrophy caused by dominant gain-of-function mutations in the gene encoding the astrocyte intermediate filament, glial fibrillary acidic protein (GFAP). However, there is an urgent need for biomarkers to assist in monitoring not only the progression of disease but also the response to treatment. GFAP is the obvious candidate for such a biomarker, as it is measurable in body fluids that are readily accessible for biopsy, namely cerebrospinal fluid and blood. However, in the case of ASOs, the treatment that is furthest in development, GFAP is the target of therapy and presumably would go down independent of disease status. Hence, there is a critical need for biomarkers that are not directly affected by the treatment strategy. Methods: We explored the potential utility of biomarkers currently being studied in other neurodegenerative diseases and injuries, specifically neurofilament light protein (NfL), phosphorylated forms of tau, and amyloid-β peptides (Aβ42/40). Results and conclusions: Here, we report that GFAP is elevated in plasma of all age groups afflicted by AxD, including those with adult onset. NfL and p-tau are also elevated, but to a much lesser extent than GFAP. In contrast, the levels of Aß40 and Aß42 are not altered in AxD.
Language	English
Publishing date	2024-04-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-024-07495-8
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