Clinical validity of cerebrospinal fluid Aβ42, tau, and phospho-tau as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework

Autor: Niklas Mattsson, Anders Lönneborg, Kaj Blennow, Oskar Hansson, Marina Boccardi
Rok vydání: 2017
Předmět:
Alzheimer Disease/diagnosis
Tau Proteins/cerebrospinal fluid
0301 basic medicine
Oncology
Aging
medicine.medical_specialty
Cognitive Dysfunction/diagnosis
Neurocognitive Disorders
tau Proteins
Context (language use)
Disease
ddc:616.89
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
Internal medicine
mental disorders
medicine
Humans
Dementia
Biomarkers/cerebrospinal fluid
Cognitive Dysfunction
Amyloid beta-Peptides
General Neuroscience
Prodromal Stage
Reproducibility of Results
medicine.disease
Amyloid beta-Peptides/cerebrospinal fluid
Peptide Fragments
Clinical trial
Dementia/diagnosis
Early Diagnosis
030104 developmental biology
Neurocognitive Disorders/diagnosis
Biomarker (medicine)
Neurology (clinical)
Peptide Fragments/cerebrospinal fluid
Geriatrics and Gerontology
Alzheimer's disease
Psychology
Neurocognitive
Neuroscience
Biomarkers
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Neurobiology of Aging, Vol. 52 (2017) pp. 196-213
ISSN: 0197-4580
DOI: 10.1016/j.neurobiolaging.2016.02.034
Popis: Novel diagnostic criteria for Alzheimer's disease (AD) incorporate biomarkers, but their maturity for implementation in clinical practice at the prodromal stage (mild cognitive impairment [MCI]) is unclear. Here, we evaluate cerebrospinal fluid (CSF) β-amyloid42 (Aβ42), total tau, and phosphorylated tau in the light of a 5-phase framework for biomarker development. Ample evidence is available for phase 1 (identifying useful leads) and phase 2 (assessing the accuracy for AD dementia versus controls) for CSF biomarkers. Phase 3 (utility in MCI) is partially achieved. In cohorts with long follow-up time, CSF Aβ42, total tau, and phosphorylated tau have high diagnostic accuracy for MCI due to AD. Phase 4 (performance in real world) is ongoing, and phase 5 studies (quantify impact and costs) are to come. Our results highlight priorities to pursue and to enable the proper use of CSF biomarkers in the clinic. Priorities are to reduce measurement variability by introduction of fully automated assay systems; to increase diagnostic specificity toward non-AD neurocognitive diseases at the MCI stage; and to clarify the role of CSF biomarkers versus other biomarker modalities in clinical practice and in design of clinical trials. These efforts are currently ongoing.
Databáze: OpenAIRE
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