Figure - available from: Alzheimer's & Dementia
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Area under the curve analysis demonstrating discriminability between Aβ‐PET positive and negative participants for each plasma biomarker. Data are shown for the overall cohort, Non‐Hispanic participants, and Hispanic participants. Plasma p‐tau181 concentrations most accurately discriminated Aβ‐PET positive and negative participants (maroon) followed by GFAP (blue) and NfL (green). Discrimination accuracy was similar for both ethnicity groups. Aβ, beta‐amyloid; GFAP, glial fibrillary acidic protein; NfL, neurofilament light; PET, positron emission tomography
Source publication
INTRODUCTION
Alzheimer's disease studies often lack ethnic diversity.
METHODS
We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p‐tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non‐amnestic MCI/dementia), and Aβ‐PET in Hispanic and non‐Hispanic older adults. His...
Citations
... The biomarkers evaluated in the study were p-tau181, GFAP, and NfL. Additionally, 240 participants completed Aβ-PET scans [131]. The results showed that p-tau181 levels were significantly higher in individuals with amnestic mild cognitive impairment (MCI) and dementia than those who were clinically normal. ...
An improved understanding of the pathobiology of Alzheimer’s disease (AD) should lead ultimately to an earlier and more accurate diagnosis of AD, providing the opportunity to intervene earlier in the disease process and to improve outcomes. The known hallmarks of Alzheimer’s disease include amyloid-β plaques and neurofibrillary tau tangles. It is now clear that an imbalance between production and clearance of the amyloid beta protein and related Aβ peptides, especially Aβ42, is a very early, initiating factor in Alzheimer’s disease (AD) pathogenesis, leading to aggregates of hyperphosphorylation and misfolded tau protein, inflammation, and neurodegeneration. In this article, we review how the AD diagnostic process has been transformed in recent decades by our ability to measure these various elements of the pathological cascade through the use of imaging and fluid biomarkers. The more recently developed plasma biomarkers, especially phosphorylated-tau217 (p-tau217), have utility for screening and diagnosis of the earliest stages of AD. These biomarkers can also be used to measure target engagement by disease-modifying therapies and the response to treatment.
Biomarkers that predict the clinical onset of Alzheimer’s disease (AD) enable the identification of individuals in the early, preclinical stages of the disease. Detecting AD at this point may allow for more effective therapeutic interventions and optimized enrollment for clinical trials of novel drugs. The current biological diagnosis of AD is based on the AT(N) classification system with the measurement of brain deposition of amyloid-β (Aβ) (“A”), tau pathology (“T”), and neurodegeneration (“N”). Diagnostic cut-offs for Aβ1–42, the Aβ1–42/Aβ1–40 ratio, tau and hyperphosphorylated-tau concentrations in cerebrospinal fluid have been defined and may support AD clinical diagnosis. Blood-based biomarkers of the AT(N) categories have been described in the AD continuum. Crosssectional and longitudinal studies have shown that the combination of blood biomarkers tracking neuroaxonal injury (neurofilament light chain) and neuroinflammatory pathways (glial fibrillary acidic protein) enhance sensitivity and specificity of AD clinical diagnosis and improve the prediction of AD onset. However, no international accepted cut-offs have been identified for these blood biomarkers. A kit for blood Aβ1–42/Aβ1–40 is commercially available in the U.S.; however, it does not provide a diagnosis, but simply estimates the risk of developing AD. Although blood-based AD biomarkers have a great potential in the diagnostic work-up of AD, they are not ready for the routine clinical use.
