Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers

JAMA Neurology, Год журнала: 2023, Номер 80(4), С. 360 - 360

Опубликована: Фев. 6, 2023

Importance Alzheimer disease (AD) pathology starts with a prolonged phase of β-amyloid (Aβ) accumulation without symptoms. The duration this differs greatly among individuals. While has high relevance for clinical trial designs, it is currently unclear how to best predict the onset progression. Objective To evaluate combinations different plasma biomarkers predicting cognitive decline in Aβ-positive cognitively unimpaired (CU) Design, Setting, and Participants This prospective population-based prognostic study evaluated data from 2 longitudinal cohort studies (the Swedish BioFINDER-1 Wisconsin Registry Prevention [WRAP]), collected February 8, 2010, October 21, 2020, August 11, 2011, June 27, 2021, WRAP cohort. were CU individuals recruited memory clinics who had brain Aβ defined by cerebrospinal fluid (CSF) Aβ42/40 Pittsburgh Compound B (PiB) positron emission tomography (PET) study. A total 564 eligible Aβ-negative participants available relevant cohorts included study; those, 171 main analyses. Exposures Baseline P-tau181, P-tau217, P-tau231, glial fibrillary filament protein, neurofilament light measured plasma; CSF cohort, PiB PET uptake Main Outcomes Measures primary outcome was measures cognition (using Mini-Mental State Examination [MMSE] modified Preclinical Cognitive Composite [mPACC]) over median 6 years (range, 2-10 years). secondary conversion AD dementia. used linear regression models rates change (calculated separately). Models adjusted age, sex, education, apolipoprotein E ε4 allele status, baseline cognition. Multivariable compared based on model R coefficients corrected Akaike information criterion. Results Among analyses, 119 (mean [SD] 73.0 [5.4] years; 60.5% female) study, 52 64.4 [4.6] 65.4% In P-tau217 marker mPACC (model = 0.41) MMSE 0.34) superior covariates-only (mPACC: 0.23; MMSE: 0.04; P < .001 both comparisons). validated cohort; example, associated slopes ( 0.13 vs 0.01 model; .01) 0.29 0.24 .046). Sparse identified as predictor decline. Power calculations enrichment hypothetical trials revealed large relative reductions sample sizes when using enrich likely experience time. Conclusions Relevance predicted patients preclinical AD. These findings suggest that may be complement or participant selection novel disease-modifying treatments.

Язык: Английский

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Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

Alzheimer s Research & Therapy, Год журнала: 2021, Номер 13(1)

Опубликована: Дек. 1, 2021

Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer's disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 Lilly), two P-tau231 (ADx, Gothenburg).We studied the analytical (sensitivity, precision, parallelism, dilution linearity, recovery) clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- sex-matched controls) performance assays.All robust performance, particularly Eli Lilly; Gothenburg all differentiate from controls, with AUCs 0.936-0.995 (P-tau231 ADx: AUC = 0.719). Results obtained Lilly assay, assay strongly correlated (Spearman's rho > 0.86), while correlations ADx results were moderate (rho < 0.65).P-tau isoforms can be measured robustly by several novel high-sensitive assays.

Язык: Английский

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Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration

Brain, Год журнала: 2022, Номер 146(3), С. 1152 - 1165

Опубликована: Дек. 27, 2022

Blood-based biomarkers for amyloid beta and phosphorylated tau show good diagnostic accuracies agreements with their corresponding CSF neuroimaging in the amyloid/tau/neurodegeneration [A/T/(N)] framework Alzheimer's disease. However, blood-based neurodegeneration marker neurofilament light is not specific to disease while total-tau shows lack of correlation total-tau. Recent studies suggest that blood originates principally from peripheral, non-brain sources. We sought address this challenge by generating an anti-tau antibody selectively binds brain-derived avoids peripherally expressed 'big tau' isoform. applied develop ultrasensitive assay tau, validated it five independent cohorts (n = 609) including a blood-to-autopsy cohort, biomarker-classified memory clinic cohorts. In paired samples, serum were significantly correlated (rho 0.85, P < 0.0001), 0.23, 0.3364). showed equivalent performance as separate biomarker-positive participants biomarker-negative controls. Furthermore, plasma accurately distinguished autopsy-confirmed other neurodegenerative diseases (area under curve 86.4%) did 54.3%). These performances presence concomitant pathologies. Plasma 0.52-0.67, 0.003), but -0.14-0.17, 0.501), was associated global regional plaque neurofibrillary tangle counts. results further verified two where differentiated range disorders, frontotemporal lobar degeneration atypical parkinsonian disorders up 99.6%). Notably, plasma/serum only diseases. Across cohorts, AT(N) cognitive function. Brain-derived new biomarker outperforms and, unlike light, specificity disease-type neurodegeneration. Thus, demonstrates potential complete scheme blood, will be useful evaluate disease-dependent processes clinical research purposes.

Язык: Английский

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The effects of protein corona on in vivo fate of nanocarriers

Advanced Drug Delivery Reviews, Год журнала: 2022, Номер 186, С. 114356 - 114356

Опубликована: Май 17, 2022

Язык: Английский

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Plasma Aβ42/40 ratio, p‐tau181, GFAP, and NfL across the Alzheimer's disease continuum: A cross‐sectional and longitudinal study in the AIBL cohort

Alzheimer s & Dementia, Год журнала: 2022, Номер 19(4), С. 1117 - 1134

Опубликована: Июль 21, 2022

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional longitudinal comparisons of the aforementioned across AD continuum lacking.Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, NfL were measured utilizing Single Molecule Array (Simoa) platform compared cross-sectionally continuum, wherein Aβ-PET (positron emission tomography)-negative cognitively unimpaired (CU Aβ-, n = 81) mild cognitive impairment (MCI 26) participants with Aβ-PET-positive Aβ+, 39; MCI 33; 46) from Australian Imaging, Biomarker & Lifestyle Flagship Study Ageing (AIBL) cohort. Longitudinal plasma biomarker changes also assessed in (n 27) 29) CU 120) participants. In addition, associations between baseline levels prospective decline load over a 7 to 10-year duration.Lower Aβ1-42/Aβ1-40 ratio elevated p-tau181 GFAP observed whereas was Aβ+ Aβ- Aβ-. Among biomarkers, models without risk factors (age, sex, apolipoprotein E (APOE) ε4 carrier status), performed equivalent or better than other predicting brain Aβ-/+ status continuum. factors, panel Aβ1-42/Aβ1-40, any alone Longitudinally, altered CU, CU. lower higher associated increased prospectively.These findings suggest that longitudinally, along prospectively load. although an may have superior predictive capability continuum.Area under curve (AUC) ≥ AUC Aβ42/40, PET (Aβ-/+). Aβ42/40+p-tau181+GFAP Aβ42/40/p-tau181/GFAP/NfL Aβ-/+. versus decline. Aβ prospectively.

Язык: Английский

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