Plasma Markers of Alzheimer's Disease Pathology, Neuronal Injury, and Astrocytic Activation and MRI Load of Vascular Pathology and Neurodegeneration: The SMART‐MR Study

Journal of the American Heart Association, Journal Year: 2024, Volume and Issue: 13(4)

Published: Feb. 14, 2024

Background Two of the main causes for dementia are Alzheimer's disease (AD) and vascular pathology, with most patients showing mixed pathology. Plasma biomarkers disease‐related pathology have recently emerged, including Aβ (amyloid‐beta), p‐tau (phosphorylated tau), NfL (neurofilament light), GFAP (glial fibrillary acidic protein). There is a current gap in literature regarding whether there an association between these plasma neurodegeneration. Methods Results Cross‐sectional data from 594 individuals (mean [SD] age: 64 [8] years; 17% female) were included SMART‐MR (Second Manifestations Arterial Disease‐Magnetic Resonance) study, prospective cohort study history arterial disease. markers assessed using single molecular array assays (Quanterix). Magnetic resonance imaging white matter hyperintensity volume, presence infarcts (yes/no), total brain hippocampal volume on 1.5T magnetic imaging. Linear regressions performed each standardized marker as separate outcomes, correcting age, sex, education, intracranial volume. Logistic lacunar cortical infarcts. Higher p‐tau181 was associated larger ( b per SD increase=0.16 [95% CI, 0.06–0.26], P =0.015). =−5.63, −8.95 to −2.31], =0.015) lower (odds ratio [OR], 1.42 1.13–1.78], =0.039). levels (OR, 1.45 1.09–1.92], =0.010). Conclusions that been tau axonal injury, astrocytic activation related imagingmarkers neurodegeneration manifest

Language: Английский

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Relationships between plasma biomarkers, tau PET, FDG PET, and volumetric MRI in mild to moderate Alzheimer's disease patients

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2024, Volume and Issue: 10(3)

Published: July 1, 2024

Abstract INTRODUCTION The “A/T/N” (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimer's disease (AD) diagnosis and can encompass additional changes such as inflammation (“I”). A spectrum of T/N/I imaging plasma biomarkers was acquired in phase 2 clinical trial rasagiline mild to moderate AD patients. We evaluated these understand biomarker distributions relationships within this population. METHODS Plasma pTau‐181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation‐related proteins, measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, volumetric magnetic resonance (MRI), cognitive endpoints were analyzed assess characteristics the overall population ( N = 47 at baseline 21 longitudinal comparisons) age‐decade subgroups (57‐69, 70‐79, 80‐90 years). RESULTS Data demonstrate wide heterogeneity influenced by age sex. pTau‐181 GFAP correlate with tau most strongly left inferior temporal cortex p 0.0002, 0.0006, respectively). In regions beyond cortex, PET uptake decreased same or concentrations. FDG brain volumes numerous (such temporal: 0.0007, 0.00001, NfL, GFAP, all modalities MMSE; subsequent MMSE decline is predicted parahippocampal lateral 0.0007) volume 0.0006). Lateral 0.006) 0.0001) are associated ADAS‐cog decline. NfL correlates but not PET. Inflammation intercorrelated correlated only youngest group. DISCUSSION Associations between biomarkers, status observed study provide insight into among processes AD. Findings show potential characterize patients regarding likely pathology, neurodegeneration, prospective decline, importance covariates age. Highlights regional global Volume showed strong one another, status. Temporal both ADAS‐cog. enrich elevated significant covariate.

Language: Английский

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Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2023, Volume and Issue: 15(2)

Published: April 1, 2023

Plasma tests have demonstrated high diagnostic accuracy for identifying Alzheimer's disease pathology. To facilitate the transition to clinical utility, we assessed whether plasma storage duration and temperature affect biomarker concentrations.

Language: Английский

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Profiling of plasma biomarkers in the context of memory assessment in a tertiary memory clinic

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 25, 2023

Abstract Plasma biomarkers have shown promising performance in research cohorts discriminating between different stages of Alzheimer’s disease (AD). Studies clinical populations are necessary to provide insights on the utility plasma before their implementation real-world settings. Here we investigated (glial fibrillary acidic protein (GFAP), tau phosphorylated at 181 and 231 (pTau181, pTau231), amyloid β (Aβ) 42/40 ratio, neurofilament light) 126 patients (age = 65 ± 8) who were admitted Clinic for Cognitive Disorders, Karolinska University Hospital. After extensive assessment (including CSF analysis), classified as: mild cognitive impairment (MCI) ( n 75), AD 25), non-AD dementia 16), no 9). To refine diagnosis, examined with [ 18 F]flutemetamol PET (Aβ-PET). Aβ-PET images visually rated positivity/negativity quantified Centiloid. Accordingly, 68 Aβ+ 54 Aβ– identified. measured using single molecule arrays (SIMOA). Receiver-operated curve (ROC) analyses performed detect Aβ-PET+ biomarkers. In whole cohort, centiloid values correlated positively GFAP, pTau231, pTau181, negatively Aβ42/40 ratio. While MCI group, only GFAP was associated Aβ centiloid. ROC analyses, among standalone biomarkers, showed highest area under compared other The combination via regression most predictive Aβ-PET, especially group (prior PET, 75) (sensitivity 100%, specificity 82%, negative value 100%). our cohort memory clinic (mainly MCI), sensitive ruling out individuals, thus suggesting a potential role as rule-out tool practice.

Language: Английский

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Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6115 - 6132

Published: Aug. 3, 2024

Abstract INTRODUCTION We developed a multimarker blood test result interpretation tool for the clinical dementia practice, including phosphorylated (P‐)tau181, amyloid‐beta (Abeta)42/40, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). METHODS measured plasma biomarkers with Simoa ( n = 1199), applied LASSO regression biomarker selection receiver operating characteristics (ROC) analyses to determine diagnostic accuracy. validated our findings in two independent cohorts constructed visualization approach. RESULTS P‐tau181, GFAP, NfL were selected. This combination had area under curve (AUC) 83% identify amyloid positivity pre‐dementia stages, AUC 87%–89% differentiate Alzheimer's or controls from frontotemporal dementia, 74%–76% Lewy bodies. Highly reproducible AUCs obtained cohorts. The resulting includes UpSet plots visualize stand‐alone results density combined. DISCUSSION Our is ready testing real‐world settings. Highlights practice. P‐tau, NfL. particularly useful diagnosis.

Language: Английский

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