Different phosphorylated tau isoforms in biochemical diagnosis of Alzheimer’s disease.

Background: In the context of Alzheimer's disease (AD), blood‐based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD.

Plasma and neuroimaging biomarkers of small vessel disease and Alzheimer’s disease in a diverse cohort.

Background: Little is known about how plasma Alzheimer’s disease (AD) biomarkers relate to neuroimaging biomarkers of cerebral small vessel disease (cSVD) in the context of neurodegeneration and AD pathology in late life.

Method: This cross‐sectional study included 251 Multi‐Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers (Aβ42/Aβ40, GFAP, NfL, p‐tau181, p‐tau217, p‐tau231; Quanterix SIMOA), MRI (neurodegeneration and cSVD), PiB (amyloid) PET, and UDSv3‐based adjudicated cognitive status (69% cognitively normal, 27% MCI, 4% probable dementia) data at the Wake Forest site. Multivariable models examined relationships among cognitive status, plasma, and neuroimaging biomarkers (covariates: age, education, race, gender, smoking status, kidney function [eGFR], APOE‐ε4, BMI; significance at p<.

Relationships between medical comorbidities and plasma biomarkers of Alzheimer's disease reflect increased pathological markers as well as biological variabilities.

Background: Plasma biomarkers for Alzheimer’s disease (AD) have demonstrated their accuracy as diagnostic tools, suggesting their impending integration into clinical practice. Medical comorbidities might not only affect AD pathological burdens but also cause variability of plasma biomarkers by affecting their transfer via blood brain barriers. In the present study, we aimed to determine which comorbidities might affect plasma biomarkers with (real effects) or without (biological variability) AD pathological burdens measured by β‐amyloid (Aβ) uptakes on PET.

The New Zealand‐Dementia Prevention Research Clinics: Plasma biomarkers and the Alzheimer’s disease continuum.

Background: Single molecule array (Simoa) technology enables the detection of Alzheimer’s disease (AD) neuropathology in blood. This study compared cross‐sectional biomarker profiles for participants from the New Zealand‐Dementia Prevention Research Clinics (NZ‐DPRCs) who spanned the continuum from healthy older adults to a clinical diagnosis of AD.

Method: NZ‐DPRC participants were clinically classified as cognitively unimpaired adults (CU, n=34), subjective cognitive decline (SCD, n=65), non‐amnestic mild cognitive impairment (single and multi‐domain, non‐aMCI, n= 23), amnestic MCI (single and multi‐domain, aMCI, n=104), and AD (n=27).

PLASMA BD‐TAU AS A SPECIFIC CORRELATE OF DISEASE SEVERITY AND DYNAMIC ACROSS THE ALZHEIMER'S DISEASE SPECTRUM.

Background: The identification of biomarkers for Alzheimer's disease (AD) remains a significant challenge, particularly for the clinical severity of the disease. Recent studies have shown that plasma brain‐derived‐tau (BD‐Tau) could be a promising biomarker for the identification of AD‐type neurodegeneration. This study aimed to investigate the potential of BD‐Tau in differentiating various clinical stages of AD, ranging from cognitively unimpaired AD to severe dementia AD.

The role of biofluid markers in predicting near‐term cognitive impairment.

Background: PET biomarkers have proven valuable for identifying cognitively unimpaired (CU) individuals at‐risk of near‐term clinical progression. Given the increasing interest in plasma biomarkers to detect Alzheimer’s pathology, we assessed levels of amyloid (Aβ) and tau (p‐tau217 and p‐tau181) biomarkers in plasma (A+T+) in CU individuals as predictors of clinical progression to mild cognitive impairment (MCI). We then repeated these analyses using cerebrospinal fluid (CSF) and PET biomarkers.

Head‐to‐head comparison of four different plasma p‐tau217 assays to detect brain amyloid pathology and cognitive decline in diverse population‐based cohorts.

Background: Plasma p‐tau217 is a highly promising biomarker for detecting Alzheimer’s disease (AD) pathology. However, it is unclear how p‐tau217 assays from different sources perform compared to one another. Moreover, studies in diverse cohorts and population‐based settings are limited.

Plasma and neuroimaging biomarkers of small vessel disease and Alzheimer’s disease in a diverse cohort.

Background: Little is known about how plasma Alzheimer’s disease (AD) biomarkers relate to neuroimaging biomarkers of cerebral small vessel disease (cSVD) in the context of neurodegeneration and AD pathology in late life.

Method: This cross‐sectional study included 251 Multi‐Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers (Aß42/Aß40, GFAP, NfL, p‐tau181, p‐tau217, p‐tau231; Quanterix SIMOA), MRI (neurodegeneration and cSVD), PiB (amyloid) PET, and UDSv3‐based adjudicated cognitive status (69% cognitively normal, 27% MCI, 4% probable dementia) data at the Wake Forest site. Multivariable models examined relationships among cognitive status, plasma, and neuroimaging biomarkers (covariates: age, education, race, gender, smoking status, kidney function [eGFR], APOE‐e4, BMI; significance at p<.

The role of biofluid markers in predicting near‐term cognitive impairment.

Background: PET biomarkers have proven valuable for identifying cognitively unimpaired (CU) individuals at‐risk of near‐term clinical progression. Given the increasing interest in plasma biomarkers to detect Alzheimer’s pathology, we assessed levels of amyloid (Aß42/40) and tau (p‐tau217 and p‐tau181) biomarkers in plasma (A+T+plasma) in CU individuals as predictors of clinical progression to mild cognitive impairment (MCI). We then repeated these analyses using cerebrospinal fluid (CSF) and PET biomarkers.

Clinical value of novel blood-based tau biomarkers in Creutzfeldt-Jakob disease.

Background: The diagnostic and prognostic performance of the novel fluid biomarkers brain-derived tau (BD-tau) and phospho-tau217 (p-tau217) in Creutzfeldt-Jakob disease (CJD) is not defined.

Methods: We measured cerebrospinal fluid (CSF) and plasma BD-tau, p-tau217, p-tau181, total tau (t-tau), neurofilament light (NfL), and 14-3-3 in 100 CJD patients, 100 with non-prion rapidly progressive dementia (np-RPD), 92 with mild cognitive impairment due to Alzheimer's disease (AD-MCI), and 55 healthy controls (HC).

Results: Plasma BD-tau performed comparably to plasma t-tau but had lower performance than CSF t-tau (p < 0.

Plasma brain-derived tau correlates with cerebral infarct volume.

Background: A blood-based biomarker that accurately reflects neuronal injury in acute ischemic stroke could be an easily accessible and cost-effective complement to clinical and radiological evaluation. Here, we investigate whether plasma levels of the novel biomarker brain-derived tau (BD-tau) reflect cerebral infarct volumes and whether BD-tau can improve clinical outcome prediction.

Methods: The present study included 713 consecutive cases from two different hospital-based cohorts, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) and SAHLSIS phase 2 (SAHLSIS2).

Plasma Alzheimer's disease biomarker variability: Amyloid-independent and amyloid-dependent factors.

Introduction: We aimed to investigate which factors affect plasma biomarker levels via amyloid beta (Aβ)-independent or Aβ-dependent effects and improve the predictive performance of these biomarkers for Aβ positivity on positron emission tomography (PET).

Methods: A total of 2935 participants underwent blood sampling for measurements of plasma Aβ42/40 ratio, phosphorylated tau 217 (p-tau217; ALZpath), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels using single-molecule array and Aβ PET. Laboratory findings were collected using a routine blood test battery.

Neuronal plasma biomarkers in acute ischemic stroke.

Early imaging-based detection of acute ischemic stroke (AIS) has improved in the era of reperfusion therapy. Despite of this, prognosis of outcome after AIS remains a challenge. Therefore, parameters that support clinical decision making are sought.

The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised for clinical use. The Alzheimer's Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in a blinded case-control study on plasma p-tau, aiming to learn which assays provide the largest fold-changes in AD compared to non-AD, have the strongest relationship between plasma and cerebrospinal fluid (CSF), and show the most consistent relationships between methods (commutability) in measuring both patient samples and candidate reference materials (CRM).

Cerebrospinal fluid p-tau181, 217, and 231 in definite Creutzfeldt-Jakob disease with and without concomitant pathologies.

Introduction: The established cerebrospinal fluid (CSF) phosphorylated tau181 (p-tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age-related tauopathy (PART) found in Creutzfeldt-Jakob disease (CJD) at autopsy.

Methods: We investigated CSF N-terminal p-tau181, p-tau217, and p-tau231 with in-house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post-mortem examination performed in patients with CJD 1.

Plasma p-tau217 predicts cognitive impairments up to ten years before onset in normal older adults.

Importance: Positron emission tomography (PET) biomarkers are the gold standard for detection of Alzheimer amyloid and tau . Such imaging can identify cognitively unimpaired (CU) individuals who will subsequently develop cognitive impartment (CI). Plasma biomarkers would be more practical than PET or even cerebrospinal fluid (CSF) assays in clinical settings.

Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.

Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status.

Association of Plasma Brain-Derived Tau With Functional Outcome After Ischemic Stroke.

Objectives: To investigate whether circulating acute-phase brain-derived tau (BD-tau) is associated with functional outcome after ischemic stroke.

Methods: Plasma tau was measured by a novel assay that selectively quantifies BD-tau in the (), which includes adult cases with ischemic stroke and controls younger than 70 years, and in an independent cohort of adult cases of all ages (). Associations with unfavorable 3-month functional outcome (modified Rankin scale score >2) were analyzed by logistic regression.

Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217.

Analytical and clinical validation of Alzheimer's disease blood biomarkers with a focus on plasma p-tau217.

Alzheimer's disease (AD) represents a growing global health challenge, necessitating accurate and reliable diagnostic methodologies for timely intervention and management. Immunoassays, specifically designed to detect biomarkers associated with AD pathology, have emerged as pivotal tools in diagnostic development. Understanding of the established protocols ensures assay sensitivity, specificity, and reproducibility, thereby enhancing the clinical utility of these diagnostic tools.

Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217.