Blood‐based biomarkers for Alzheimer's disease

EMBO Molecular Medicine, Год журнала: 2021, Номер 14(1)

Опубликована: Дек. 3, 2021

Язык: Английский

---

Blood biomarkers for Alzheimer’s disease in clinical practice and trials

Nature Aging, Год журнала: 2023, Номер 3(5), С. 506 - 519

Опубликована: Май 18, 2023

Язык: Английский

---

Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility

Nature Reviews Neurology, Год журнала: 2022, Номер 18(7), С. 400 - 418

Опубликована: Май 18, 2022

Язык: Английский

---

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

Frontiers in Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Сен. 27, 2021

Biomarkers of neurodegeneration and neuronal injury have the potential to improve diagnostic accuracy, disease monitoring, prognosis, measure treatment efficacy. Neurofilament proteins (NfPs) are well suited as biomarkers in these contexts because they major neuron-specific components that maintain structural integrity sensitive across a wide range neurologic diseases. Low levels NfPs constantly released from neurons into extracellular space ultimately reach cerebrospinal fluid (CSF) blood under physiological conditions throughout normal brain development, maturation, aging. NfP CSF rise above response independently cause. measured by lumbar puncture about 40-fold more concentrated than healthy individuals. New ultra-sensitive methods now allow minimally invasive measurement low serum or plasma track onset progression neurological disorders nervous system assess responses therapeutic interventions. Any five Nf subunits – neurofilament light chain (NfL), medium (NfM), heavy (NfH), alpha-internexin (INA) peripherin (PRPH) may be altered given neuropathological condition. In familial sporadic Alzheimer’s (AD), NfL early 22 years before clinical AD 10 AD. The determinants elevated degradation fragments magnitude damaged degenerating axons fiber tracks, affected axon caliber sizes rate release at different stages condition directly indirectly affecting central (CNS) and/or peripheral (PNS). rapidly emerging transformative neurology providing novel insights diseases advancing trials. Here we summarize current understanding intracellular physiology, pathophysiology kinetics biofluids review value limitations injury.

Язык: Английский

---

Biomarker modeling of Alzheimer’s disease using PET-based Braak staging

Nature Aging, Год журнала: 2022, Номер 2(6), С. 526 - 535

Опубликована: Апрель 25, 2022

Abstract Gold-standard diagnosis of Alzheimer’s disease (AD) relies on histopathological staging systems. Using the topographical information from [ 18 F]MK6240 tau positron-emission tomography (PET), we applied Braak system to 324 living individuals. We used PET-based stage model trajectories amyloid-β, phosphorylated (pTau) in cerebrospinal fluid (pTau 181 , pTau 217 231 and 235 ) plasma ), neurodegeneration cognitive symptoms. identified nonlinear AD biomarker corresponding spatial extent tau-PET, with modest changes detectable by II significant occurring at stages III–IV, followed plateaus. Early were associated isolated memory impairment, whereas V–VI incompatible normal cognition. In 159 individuals follow-up progression beyond III took place uniquely presence amyloid-β positivity. Our findings support as a framework natural history monitor severity humans.

Язык: Английский

---

Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes

JAMA Neurology, Год журнала: 2021, Номер 78(9), С. 1108 - 1108

Опубликована: Июль 26, 2021

Cerebrospinal fluid phosphorylated tau (p-tau) 181, p-tau217, and p-tau231 are associated with neuropathological outcomes, but a comparison of these p-tau isoforms in blood samples is needed.To conduct head-to-head plasma p-tau181 measured on the single-molecule array (Simoa) platform p-tau217 Meso Scale Discovery (MSD) amyloid positron emission tomography (PET) measures, neurodegeneration, vascular pathology, cognitive outcomes.This study included data from Mayo Clinic Study Aging collected March 1, 2015, to September 30, 2017, analyzed between December 15, 2020, May 17, 2021. Associations 4 measures dichotomous PET, metaregion interest entorhinal cortex PET were using logistic regression models; predictive accuracy was summarized area under receiver operating characteristic curve (AUROC) statistic. Of 1329 participants without dementia MSD, 200 Simoa magnetic resonance imaging at same visit eligible.Primary outcomes (greater than 1.48 standardized uptake value ratio) white matter hyperintensities, microstructural integrity (fractional anisotropy genu corpus callosum hippocampal cingulum bundle), cognition.Of participants, 101 (50.5%) male, median (interquartile range [IQR]) age 79.5 (71.1-84.1) years. A total 177 cognitively unimpaired (CU) 23 had mild impairment. Compared amyloid-negative CU among amyloid-positive (IQR) measure 49% higher (2.58 [2.00-3.72] vs 1.73 [1.45-2.13] pg/mL), MSD 53% (1.22 [0.91-1.56] 0.80 [0.66-0.97] 77% (0.23 [0.17-0.34] 0.13 [0.09-0.18] (20.21 [15.60-25.41] 14.27 [11.27-18.10] pg/mL). There no differences species for metaregions interest. However, both more accurately predicted abnormal (MSD p-tau181: AUROC, 0.70; P = .046; p-tau217: 0.81 .04). p-tau181, not p-tau231, greater hyperintensity volume lower integrity.In this largely presymptomatic population, results suggest subtle across platforms prediction cerebrovascular Alzheimer-related pathology.

Язык: Английский

---

Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease

Nature Medicine, Год журнала: 2023, Номер 29(7), С. 1775 - 1781

Опубликована: Май 29, 2023

Abstract An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological phosphorylation. Here, biomarker study across three cohorts ( n = 1,016), we tested whether astrocyte reactivity modulates association with phosphorylation CU individuals. We found was associated increased plasma phosphorylated only positive (Ast + ). Cross-sectional and longitudinal tau–positron emission tomography analyses revealed an AD-like pattern tangle accumulation as function Ast Our findings suggest important upstream event linking initial pathology, which may have implications biological definition preclinical AD selecting trials.

Язык: Английский

---

Plasma biomarkers for Alzheimer’s Disease in relation to neuropathology and cognitive change

Acta Neuropathologica, Год журнала: 2022, Номер 143(4), С. 487 - 503

Опубликована: Фев. 23, 2022

Plasma biomarkers related to amyloid, tau, and neurodegeneration (ATN) show great promise for identifying these pathological features of Alzheimer's Disease (AD) as shown by recent clinical studies selected autopsy studies. We have evaluated ATN plasma in a series 312 well-characterized longitudinally followed research subjects with available within 5 years or less before examined relation spectrum AD pathologies. Aβ42, Aβ40, total Tau, P-tau181, P-tau231 neurofilament light (NfL) were measured using Single molecule array (Simoa) assays. Neuropathological findings assessed standard protocols. Comparing pathology diagnoses ratings, we found that P-tau181 (AUC = 0.856) 0.773) showed the strongest overall sensitivity specificity neuropathological change (ADNC). increases at earlier ADNC stages than other biomarkers. Aβ42/40 was decreased amyloid pathology, modest diagnostic accuracy 0.601). NfL increased non-AD cases subset those ADNC. did not changes Lewy body disease (LBD), hippocampal sclerosis aging (HS) limbic-predominant age-related TDP-43 encephalopathy (LATE) unless present. Higher levels 231 predicted faster cognitive decline, early 10 prior autopsy, even among people normal cognition mild impairment. These results support also can help predict future predementia stages. Although consistently shows several neurological disorders, it had utility decline. this study relatively weak predictor different assay methods may be needed improve on this. Additional are detect presence impact LBD LATE pathology.

Язык: Английский

---

Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2021, Номер 18(6), С. 1141 - 1154

Опубликована: Сен. 8, 2021

Abstract Introduction This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential plasma glial fibrillary acidic protein (GFAP), total tau (t‐tau), phosphorylated (p‐tau181 p‐tau231), neurofilament light (NFL) in preclinical Alzheimer's disease (AD). Methods Plasma proteins were measured using Simoa assays cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) brain amyloidosis. Results GFAP, t‐tau, p‐tau181, p‐tau231 concentrations higher Aβ+ CU compared Aβ− cross‐sectionally. GFAP had highest effect size area under curve (AUC) differentiating between CU; however, no statistically significant differences observed AUCs p‐tau231, but all significantly than AUC NFL, was t‐tau. The combination base model (BM), comprising AD risk factors, age, sex, apolipoprotein E gene ( APOE ) ε4 status to have (>90%) BM any other investigated current study. Longitudinal analyses showed increased p‐tau181 NFL CU, over 12‐month duration. correlations cognition, whereas hippocampal volume. Discussion These findings highlight p‐tau for AD.

Язык: Английский

---

Advances in the development of new biomarkers for Alzheimer’s disease

Translational Neurodegeneration, Год журнала: 2022, Номер 11(1)

Опубликована: Апрель 21, 2022

Alzheimer's disease (AD) is a complex, heterogeneous, progressive and the most common type of neurodegenerative dementia. The prevalence AD expected to increase as population ages, placing an additional burden on national healthcare systems. There large need for new diagnostic tests that can detect at early stage with high specificity relatively low cost. development modern analytical tools has made it possible determine several biomarkers specificity, including pathogenic proteins, markers synaptic dysfunction, inflammation in blood. considerable potential using microRNA (miRNA) AD, studies based miRNA panels suggest could potentially be determined accuracy individual patients. Studies retina improved methods visualization fundus are also showing promising results diagnosis disease. This review focuses recent developments blood, plasma, ocular AD.

Язык: Английский

---