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- Du, Lianlian, et al.
(författare)
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Longitudinal plasma phosphorylated-tau217 and other related biomarkers in a non-demented Alzheimer's risk-enhanced sample
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD). METHODS Serial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated-tau217 (p-tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.6% with known amyloid status were amyloid positive (A+); 97.2% were cognitively unimpaired (CU). RESULTS In the CU, amyloid-negative (A-) subset, plasma p-tau217 levels increased modestly with age but were unaffected by body mass index and kidney function. In the whole sample, average p-tau217 change rates were higher in those who were A+ (e.g., simple slopes(se) for A+ and A- at age 60 were 0.232(0.028) and 0.038(0.013))). High baseline p-tau217 levels predicted faster preclinical cognitive decline. DISCUSSION p-tau217 stands out among markers for its strong association with disease and cognitive decline, indicating its potential for early AD detection and monitoring progression. HIGHLIGHTS Phosphorylated-tau217 (p-tau217) trajectories were significantly different in people who were known to be amyloid positive. Subtle age-related trajectories were seen for all the plasma markers in amyloid-negative cognitively unimpaired. Kidney function and body mass index were not associated with plasma p-tau217 trajectories. Higher plasma p-tau217 was associated with faster preclinical cognitive decline.
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2. |
- Ashton, Nicholas J., et al.
(författare)
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Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology
- 2024
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Ingår i: JAMA NEUROLOGY. - 2168-6149 .- 2168-6157.
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Tidskriftsartikel (refereegranskat)abstract
- ImportancePhosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. ObjectiveTo determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid beta (A beta) and longitudinal change across 3 selected cohorts. Design, Setting, and ParticipantsThis cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017-August 2021) and Wisconsin Registry for Alzheimer's Prevention (WRAP) cohort (visits February 2007-November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009-November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023. ExposuresMagnetic resonance imaging, A beta positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (A beta 42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay). Main Outcomes and MeasuresAccuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status. ResultsThe study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated A beta (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal A beta pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in A beta-positive individuals, with the highest increase observed in those with tau positivity. Conclusions and RelevanceThis study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.
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3. |
- Hale, Madeline R, et al.
(författare)
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Associations between recall of proper names in story recall and CSF amyloid and tau in adults without cognitive impairment.
- 2024
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Ingår i: Neurobiology of aging. - 1558-1497. ; 133, s. 87-98
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Tidskriftsartikel (refereegranskat)abstract
- Neuropsychological measures sensitive to decline in the preclinical phase of Alzheimer's diseaseare needed. We previously demonstrated that higher amyloid-beta (Aβ) assessed by positron emission tomography in adults without cognitive impairment was associated with recall of fewer proper names in Logical Memory story recall. The current study investigated the association between proper names and cerebrospinal fluidbiomarkers (Aβ42/40, phosphorylated tau181 [pTau181], neurofilament light) in 223 participants from the Wisconsin Registry for Alzheimer's Prevention. We assessed associations between biomarkers and delayed Logical Memory total score and proper names using binary logistic regressions. Sensitivity analyses used multinomial logistic regression and stratified biomarker groups. Lower Logical Memory total score and proper names scores from themost recent visit were associated with biomarker positivity. Relatedly, there was a 27% decreased risk of being classified Aβ42/40+/pTau181+for each additional proper name recalled. A linear mixed effects model found that longitudinal change in proper names recall was predicted by biomarker status. These results demonstrate a novel relationship between proper names and Alzheimer's disease-cerebrospinal fluid pathology.
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