Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers

Bateman, Randall J.; Christian, Bradley T.; Price, Julie C.; Laymon, Charles M.; Schupf, Nicole; Klunk, William E.; Lott, Ira T.; Silverman, Wayne; Rosas, H. Diana; Zaman, Shahid; Mapstone, Mark; Lai, Florence; Ances, Beau M.; Handen, Benjamin L.; Hansson, Oskar

doi:10.1001/jamaneurol.2022.1740

Cited by 22 publications

(29 citation statements)

References 45 publications

(86 reference statements)

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“…In adults with Down syndrome (which can be characterized by triplication of the APP gene), plasma p-tau181 and p-tau217 discriminated asymptomatic individuals from each of the prodromal and dementia groups [54,55]. Since a large proportion of people with Down syndrome develop AD symptomatology and pathology during their lives, evaluating biomarker changes in these individuals provides key insights into the biological progression and staging that is important for understanding same in sporadic cases.…”

Section: Plasma P-tau Levels In Individuals With Genetic Predispositi...mentioning

confidence: 99%

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

González‐Ortiz

Kac

Brum

et al. 2023

Mol Neurodegeneration

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As the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, and healthcare systems. Although AD can be identified and diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence and clinical symptoms, challenges regarding practicality and accessibility hinder their widespread availability and implementation. Consequently, many people with suspected cognitive impairment due to AD do not receive a biomarker-supported diagnosis. Blood biomarkers have the capacity to help expand access to AD diagnostics worldwide. One such promising biomarker is plasma phosphorylated tau (p-tau), which has demonstrated specificity to AD versus non-AD neurodegenerative diseases, and will be extremely important to inform on clinical diagnosis and eligibility for therapies that have recently been approved. This review provides an update on the diagnostic and prognostic performances of plasma p-tau181, p-tau217 and p-tau231, and their associations with in vivo and autopsy-verified diagnosis and pathological hallmarks. Additionally, we discuss potential applications and unanswered questions of plasma p-tau for therapeutic trials, given their recent addition to the biomarker toolbox for participant screening, recruitment and during-trial monitoring. Outstanding questions include assay standardization, threshold generation and biomarker verification in diverse cohorts reflective of the wider community attending memory clinics and included in clinical trials.

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Section: Plasma P-tau Levels In Individuals With Genetic Predispositi...mentioning

confidence: 99%

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

González‐Ortiz

Kac

Brum

et al. 2023

Mol Neurodegeneration

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“…However, NfL levels increase in normal aging and many other CNS disorders including Down’s syndrome with no clinical evidence of AD. Therefore, it is a nonspecific marker for neurodegeneration [ 38 ].…”

Section: Blood Biomarkers Of Neuronal Injury and Neurodegenerationmentioning

confidence: 99%

Experimental and Clinical Biomarkers for Progressive Evaluation of Neuropathology and Therapeutic Interventions for Acute and Chronic Neurological Disorders

Reddy

Abeygunaratne

2022

IJMS

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This article describes commonly used experimental and clinical biomarkers of neuronal injury and neurodegeneration for the evaluation of neuropathology and monitoring of therapeutic interventions. Biomarkers are vital for diagnostics of brain disease and therapeutic monitoring. A biomarker can be objectively measured and evaluated as a proxy indicator for the pathophysiological process or response to therapeutic interventions. There are complex hurdles in understanding the molecular pathophysiology of neurological disorders and the ability to diagnose them at initial stages. Novel biomarkers for neurological diseases may surpass these issues, especially for early identification of disease risk. Validated biomarkers can measure the severity and progression of both acute neuronal injury and chronic neurological diseases such as epilepsy, migraine, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis, and other brain diseases. Biomarkers are deployed to study progression and response to treatment, including noninvasive imaging tools for both acute and chronic brain conditions. Neuronal biomarkers are classified into four core subtypes: blood-based, immunohistochemical-based, neuroimaging-based, and electrophysiological biomarkers. Neuronal conditions have progressive stages, such as acute injury, inflammation, neurodegeneration, and neurogenesis, which can serve as indices of pathological status. Biomarkers are critical for the targeted identification of specific molecules, cells, tissues, or proteins that dramatically alter throughout the progression of brain conditions. There has been tremendous progress with biomarkers in acute conditions and chronic diseases affecting the central nervous system.

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“… What are the characteristics of the nervous system that are different (see Challenge 2) at the onset [ 113 ] of pathological aging? What is the detailed temporal relationship between amyloid and tau pathology, and the various biomarkers and behavioral changes in the database [ 114 , 115 , 116 ]? …”

Section: Specific Challengesmentioning

confidence: 99%

“…What is the detailed temporal relationship between amyloid and tau pathology, and the various biomarkers and behavioral changes in the database [ 114 , 115 , 116 ]?…”

Section: Specific Challengesmentioning

confidence: 99%

A Perspective: Challenges in Dementia Research

Stecker

2022

Medicina

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Although dementia is a common and devastating disease that has been studied intensely for more than 100 years, no effective disease modifying treatment has been found. At this impasse, new approaches are important. The purpose of this paper is to provide, in the context of current research, one clinician’s perspective regarding important challenges in the field in the form of specific challenges. These challenges not only illustrate the scope of the problems inherent in finding treatments for dementia, but can also be specific targets to foster discussion, criticism and new research. One common theme is the need to transform research activities from small projects in individual laboratories/clinics to larger multinational projects, in which each clinician and researcher works as an integral part. This transformation will require collaboration between researchers, large corporations, regulatory/governmental authorities and the general population, as well as significant financial investments. However, the costs of transforming the approach are small in comparison with the cost of dementia.

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Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers

Cited by 22 publications

References 45 publications

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

Experimental and Clinical Biomarkers for Progressive Evaluation of Neuropathology and Therapeutic Interventions for Acute and Chronic Neurological Disorders

A Perspective: Challenges in Dementia Research

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