Validation of Plasma Amyloid-β 42/40 for Detecting Alzheimer Disease Amyloid Plaques

Neurology, Год журнала: 2021, Номер 98(7)

Опубликована: Дек. 14, 2021

To determine the diagnostic accuracy of a plasma Aβ42/Aβ40 assay in classifying amyloid PET status across global research studies using samples collected by multiple centers that utilize different blood collection and processing protocols.

Язык: Английский

---

Blood-based biomarkers for Alzheimer’s disease: Current state and future use in a transformed global healthcare landscape

Neuron, Год журнала: 2023, Номер 111(18), С. 2781 - 2799

Опубликована: Июнь 8, 2023

Язык: Английский

---

Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies

Chemical Society Reviews, Год журнала: 2021, Номер 51(2), С. 513 - 565

Опубликована: Дек. 10, 2021

We discuss novel approaches for embracing and reproducing complexity of Tau pathology required developing disease-relevant diagnostics effective therapies.

Язык: Английский

---

Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2021, Номер 18(4), С. 824 - 857

Опубликована: Сен. 28, 2021

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has accumulated 15 years of clinical, neuroimaging, cognitive, biofluid biomarker and genetic data, samples available to researchers, resulting in more than 3500 publications. This review covers studies from 2018 2020.

Язык: Английский

---

The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer’s disease: a literature review

Alzheimer s Research & Therapy, Год журнала: 2022, Номер 14(1)

Опубликована: Дек. 27, 2022

Abstract The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark Alzheimer’s disease (AD). Detection Aβ pathology essential for AD diagnosis and identifying recruiting research participants clinical trials evaluating disease-modifying therapies. Currently, diagnoses are usually made by assessments, although detection with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used specialty clinics. These measures aggregation, e.g. plaques, protofibrils, oligomers, medically invasive often only available at specialized medical centers not covered insurance, PET costly. Therefore, major goal recent years has been to identify blood-based biomarkers that accurately detect cost-effective, minimally procedures. To assess performance plasma assays predicting burden central nervous system (CNS), this review compares twenty-one different manuscripts measurements 42 40 amino acid-long (Aβ42 Aβ40) predict CNS status. Methodologies quantitate Aβ42 peptides blood via immunoassay immunoprecipitation-mass spectrometry (IP-MS) were considered, their ability distinguish amyloidosis compared CSF as reference standards was evaluated. Recent studies indicate some IP-MS perform well precisely measuring detecting aggregates.

Язык: Английский

---

Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Фев. 2, 2022

Abstract Background One of the key pathological hallmarks Alzheimer disease (AD) is accumulation amyloid-β (Aβ) peptide into amyloid plaques. The apolipoprotein E ( APOE ) gene strongest genetic risk factor for late-onset AD and has been shown to influence Aβ in brain an isoform-dependent manner. ApoE can be produced by different cell types brain, with astrocytes being largest producer apoE, although reactive microglia also express high levels apoE. While studies have that altering apoE development plaque pathology, it not fully known how specific types, such as astrocytes, contributes pathology. Methods We utilized knock-in mice capable having selectively removed from a tamoxifen-inducible manner crossed them APP/PS1-21 mouse model amyloidosis. analyzed changes assessed impact on cellular responses plaques when astrocytic removed. Results Tamoxifen administration was strongly reducing markedly astrocyte while microglial expression remained. Reduction apoE3 apoE4 led large decrease deposition less compact overall Iba1 + were unchanged cortex after disease-associated markers Clec7a lower around plaques, indicating decreased activation. Additionally, GFAP are but reduced female reduction Finally, amount neuritic dystrophy remaining individual increased removal cortical amyloid-associated significantly decreased. Conclusion This study reveals important role well certain Aβ-associated downstream effects.

Язык: Английский

---

Blood Biomarkers from Research Use to Clinical Practice: What Must Be Done? A Report from the EU/US CTAD Task Force

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2022, Номер unknown

Опубликована: Янв. 1, 2022

Язык: Английский

---

Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Год журнала: 2022, Номер 14(1)

Опубликована: Янв. 1, 2022

We explored what combination of blood-based biomarkers (amyloid beta [Aβ]1-42/1-40, phosphorylated tau [p-tau]181, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) differentiates Alzheimer's disease (AD) dementia, frontotemporal dementia (FTD), and with Lewy bodies (DLB). measured the Simoa in two separate cohorts (n = 160 n 152). In one cohort, Aβ1-42/1-40 was also mass spectrometry (MS). assessed differential diagnostic value markers, by logistic regression Wald's backward selection. MS similarly differentiated AD from controls. The panel that optimally FTD consisted NfL p-tau181 (area under curve [AUC] 0.94; cohort 1) or NfL, GFAP, (AUC 0.90; 2). For DLB, p-tau181, GFAP 0.88; 1), only 0.81; A plasma but not Aβ1-42/1-40, might be useful to discriminate AD, FTD, DLB.

Язык: Английский

---

Blood biomarkers for the diagnosis of amnestic mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis

Neuroscience & Biobehavioral Reviews, Год журнала: 2021, Номер 128, С. 479 - 486

Опубликована: Июль 7, 2021

Язык: Английский

---

Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort

Neurology, Год журнала: 2022, Номер 100(5)

Опубликована: Окт. 19, 2022

Blood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET and effectively discriminate AD from other neurodegenerative diseases. Our aim was test their utility in clinical practice, a multicentric unselected prospective cohort where patients presented large spectrum of cognitive deficits complaints. The MEMENTO enrolled 2,323 outpatients subjective complaint (SCC) mild impairment (MCI) consulting 26 French memory clinics. Participants had neuropsychological assessments, MRI, blood sampling at baseline. amyloid were optional. Baseline Aβ42/40 ratio, total tau, p181-tau, neurofilament light chain (NfL) measured using Simoa HD-X analyzer. An expert committee validated incident dementia cases during 5-year follow-up period. Overall, 2,277 individuals least 1 baseline biomarker available (n = 357 subsample, n 649 subsample), among whom 257 diagnosed AD/mixed follow-up. All but tau mildly correlated equivalence the (r 0.33 0.46, p < 0.0001) amyloid-PET status (p 0.0001). p181-tau best identify positivity (area under curve 0.74 [95% CI 0.69; 0.79]). Higher NfL concentrations accelerated time onset similar incidence rates, whereas less efficient than Aβ42/40. alone predictor risk (c-index 0.73 0.77]); its accuracy higher rating (CDR) 0 0.83 0.97]) CDR 0.5 0.70 0.66; 0.74]). A "clinical" reference model (combining demographics assessment) predicted c-index 0.88 0.86-0.91] performance increased 0.90 0.88; 0.92] when adding + "research" (clinical apolipoprotein E genotype signature on MRI) 0.91 0.89-0.93] increasing 0.92 0.90; 0.93] Chronic kidney vascular comorbidities did not affect predictive performances. In clinic-based SCC MCI, may good hallmarks underlying pathology add little prediction models including traditional predictors.

Язык: Английский

---