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Research papers on Alzheimer’s disease biomarkers

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  1. The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

    Guy M. McKhann, David S. Knopman, Howard Chertkow, et al. · 2011 · Alzheimer s & Dementia · 18,902 citations

    The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of expe

  2. NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease

    Clifford R. Jack, David A. Bennett, Kaj Blennow, et al. · 2018 · Alzheimer s & Dementia · 10,511 citations

    In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be document

  3. Lecanemab in Early Alzheimer’s Disease

    Christopher H. van Dyck, Chad J. Swanson, Paul Aisen, et al. · 2022 · New England Journal of Medicine · 5,344 citations

    BACKGROUND: The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer's disease. METHODS: We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer's disease (mild cognitive impairment or mild dementia due to Alzheimer's disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive i

  4. Diagnosis and management of dementia with Lewy bodies

    Ian G. McKeith, Bradley F. Boeve, Dennis W. Dickson, et al. · 2017 · Neurology · 4,481 citations

    The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123 iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic,

  5. Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease

    Randall J. Bateman, Chengjie Xiong, Tammie L.S. Benzinger, et al. · 2012 · New England Journal of Medicine · 3,849 citations

    BACKGROUND: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calcu

  6. Neuropathological Alterations in Alzheimer Disease

    Alberto Serrano‐Pozo, Matthew P. Frosch, Eliezer Masliah, et al. · 2011 · Cold Spring Harbor Perspectives in Medicine · 3,396 citations

    The neuropathological hallmarks of Alzheimer disease (AD) include "positive" lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between "normal" aging and AD dement

  7. The neuropathological diagnosis of Alzheimer’s disease

    Michael DeTure, Dennis W. Dickson · 2019 · Molecular Neurodegeneration · 3,359 citations

    Alzheimer's disease is a progressive neurodegenerative disease most often associated with memory deficits and cognitive decline, although less common clinical presentations are increasingly recognized. The cardinal pathological features of the disease have been known for more than one hundred years, and today the presence of these amyloid plaques and neurofibrillary tangles are still required for a pathological diagnosis. Alzheimer's disease is the most common cause of dementia globally. There remain no effective treatment options for the great majority of patients, and the primary causes of the disease are unknown except in a small number of familial cases driven by genetic mutations. Confo

  8. Donanemab in Early Symptomatic Alzheimer Disease

    John R. Sims, Jennifer A. Zimmer, Cynthia Evans, et al. · 2023 · JAMA · 2,648 citations

    Importance: There are limited efficacious treatments for Alzheimer disease. Objective: To assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque. Design, Setting, and Participants: Multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023). Interventions: Participants were rand

  10. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers

    Clifford R. Jack, David A. Bennett, Kaj Blennow, et al. · 2016 · Neurology · 1,893 citations

    Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the "A/T/N" system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. "A" refers to the value of a b-amyloid biomarker (amyloid PET or CSF Ab 42 ); "T," the value of a tau biomarker (CSF phospho tau, or tau PET); and "N," biomarkers of neurodegeneration or neuronal injury ([ 18 F]

  12. Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers.

    G. Frisoni, M. Boccardi, F. Barkhof, et al. · 2017 · The Lancet. Neurology · 568 citations

    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. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers

  15. Early diagnosis of Alzheimer's disease: the role of biomarkers including advanced EEG signal analysis. Report from the IFCN-sponsored panel of experts.

    P. M. Rossini, R. Iorio, F. Vecchio, et al. · 2020 · Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 194 citations

    Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of

  16. AI-Driven Innovations in Alzheimer's Disease: Integrating Early Diagnosis, Personalized Treatment, and Prognostic Modelling.

    Mayur B. Kale, N. Wankhede, Rupali S. Pawar, et al. · 2024 · Ageing research reviews · 145 citations

    Alzheimer's disease (AD) presents a significant challenge in neurodegenerative research and clinical practice due to its complex etiology and progressive nature. The integration of artificial intelligence (AI) into the diagnosis, treatment, and prognostic modelling of AD holds promising potential to transform the landscape of dementia care. This review explores recent advancements in AI applications across various stages of AD management. In early diagnosis, AI-enhanced neuroimaging techniques, including MRI, PET, and CT scans, enable precise detection of AD biomarkers. Machine learning models analyze these images to identify patterns indicative of early cognitive decline. Additionally, AI a

  17. Neuroinflammatory Processes, A1 Astrocyte Activation and Protein Aggregation in the Retina of Alzheimer’s Disease Patients, Possible Biomarkers for Early Diagnosis

    A. Grimaldi, N. Pediconi, Francesca Oieni, et al. · 2019 · Frontiers in Neuroscience · 138 citations

    Alzheimer’s disease (AD), a primary cause of dementia in the aging population, is characterized by extracellular amyloid-beta peptides aggregation, intracellular deposits of hyperphosphorylated tau, neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure; therefore, the actual challenge is to define new biomarkers and non-invasive technologies to measure neuropathological changes in vivo at pre-symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological

  18. Biomarkers for Alzheimer’s Disease Early Diagnosis

    Eva Ausó, V. Gómez-Vicente, Gema Esquiva · 2020 · Journal of Personalized Medicine · 124 citations

    Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Bra

  19. Retinal biomarkers for Alzheimer’s disease and vascular cognitive impairment and dementia (VCID): implication for early diagnosis and prognosis

    C. Czakó, T. Kovács, Z. Ungvari, et al. · 2020 · GeroScience · 115 citations

    Cognitive impairment and dementia are major medical, social, and economic public health issues worldwide with significant implications for life quality in older adults. The leading causes are Alzheimer’s disease (AD) and vascular cognitive impairment/dementia (VCID). In both conditions, pathological alterations of the cerebral microcirculation play a critical pathogenic role. Currently, the main pathological biomarkers of AD—β-amyloid peptide and hyperphosphorylated tau proteins—are detected either through cerebrospinal fluid (CSF) or PET examination. Nevertheless, given that they are invasive and expensive procedures, their availability is limited. Being part of the central nervous system,

  20. Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through RNA sequencing analysis

    D. Shigemizu, Taiki Mori, Shintaro Akiyama, et al. · 2020 · Alzheimer's Research & Therapy · 78 citations

    With demographic shifts toward older populations, the number of people with dementia is steadily increasing. Alzheimer’s disease (AD) is the most common cause of dementia, and no curative treatment is available. The current best strategy is to delay disease progression and to practice early intervention to reduce the number of patients that ultimately develop AD. Therefore, promising novel biomarkers for early diagnosis are urgently required. To identify blood-based biomarkers for early diagnosis of AD, we performed RNA sequencing (RNA-seq) analysis of 610 blood samples, representing 271 patients with AD, 91 cognitively normal (CN) adults, and 248 subjects with mild cognitive impairment (MCI

  21. Advances in retina imaging as potential biomarkers for early diagnosis of Alzheimer’s disease

    Ying Zhang, Yanjiang Wang, Ce Shi, et al. · 2021 · Translational Neurodegeneration · 74 citations

    As the most common form of dementia, Alzheimer’s disease (AD) is characterized by progressive cognitive impairments and constitutes a major social burden. Currently, the invasiveness and high costs of tests have limited the early detection and intervention of the disease. As a unique window of the brain, retinal changes can reflect the pathology of the brain. In this review, we summarize current understanding of retinal structures in AD, mild cognitive impairment (MCI) and preclinical AD, focusing on neurodegeneration and microvascular changes measured using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) technologies. The literature suggests that the i

  22. Biomarkers for early diagnosis of Alzheimer disease: ‘ALZheimer ASsociated gene’– a new blood biomarker?

    K. A. Jellinger, Bernd Janetzky, Johannes Attems, et al. · 2008 · Journal of Cellular and Molecular Medicine · 70 citations

    Simple, non-invasive tests for an early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers (plasma/serum, platelets, urine, connective tissue) for the early diagnosis of Alzheimer disease (AD) are available. In disease stages with evident cognitive disturbances, the clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. Diagnostic sensitivity and specificity even in early disease stages are improved by CSF markers, in particular combined tau and amyloid beta peptides (Abeta) and plasma markers (eg, Abeta-42/Abeta-40 r

  23. CSF Biomarkers in the Early Diagnosis of Mild Cognitive Impairment and Alzheimer’s Disease

    Vasileios Papaliagkas, K. Kalinderi, P. Vareltzis, et al. · 2023 · International Journal of Molecular Sciences · 59 citations

    Alzheimer’s disease (AD) is a rapidly growing disease that affects millions of people worldwide, therefore there is an urgent need for its early diagnosis and treatment. A huge amount of research studies are performed on possible accurate and reliable diagnostic biomarkers of AD. Due to its direct contact with extracellular space of the brain, cerebrospinal fluid (CSF) is the most useful biological fluid reflecting molecular events in the brain. Proteins and molecules that reflect the pathogenesis of the disease, e.g., neurodegeneration, accumulation of Abeta, hyperphosphorylation of tau protein and apoptosis may be used as biomarkers. The aim of the current manuscript is to present the most

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