Dataset Information

Plasma p-tau₁₈₁ shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.

ABSTRACT:

Introduction

We examined the ability of plasma hyperphosphorylated tau (p-tau)₁₈₁ to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL).

Methods

Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables.

Results

Plasma p-tau₁₈₁ discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau₁₈₁ had a direct association with cognitive diagnosis in a bootstrapped GGM.

Discussion

These results support plasma p-tau₁₈₁ for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.

SUBMITTER: Frank B

PROVIDER: S-EPMC9160800 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Plasma p-tau<sub>181</sub> shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.

Frank Brandon B Ally Madeline M Brekke Bailee B Zetterberg Henrik H Blennow Kaj K Sugarman Michael A MA Ashton Nicholas J NJ Karikari Thomas K TK Tripodis Yorghos Y Martin Brett B Palmisano Joseph N JN Steinberg Eric G EG Simkina Irene I Turk Katherine W KW Budson Andrew E AE O'Connor Maureen K MK Au Rhoda R Goldstein Lee E LE Jun Gyungah R GR Kowall Neil W NW Stein Thor D TD McKee Ann C AC Killiany Ronald R Qiu Wei Qiao WQ Stern Robert A RA Mez Jesse J Alosco Michael L ML

Alzheimer's & dementia : the journal of the Alzheimer's Association 20211202 8

<h4>Introduction</h4>We examined the ability of plasma hyperphosphorylated tau (p-tau)<sub>181</sub> to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL).<h4>Methods</h4>Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial re ...[more]

PMID: 34854549

Similar Datasets

Project description:BackgroundChronic heart failure (HF) is known to increase the risk of developing Alzheimer's dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood.MethodsWithin the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI).ResultsSerum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = - 0.21; p = 0.013) and pTau (ρ = - 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = - 2.4 for pTau; T = - 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = - 3.1).ConclusionspTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers.

Project description:BackgroundBlood neurofilament light (Nfl) and total-tau (t-tau) have been described to be increased in several neurological conditions, including prion diseases and other neurodegenerative dementias. Here, we aim to determine the accuracy of plasma Nfl and t-tau in the differential diagnosis of neurodegenerative dementias and their potential value as prognostic markers of disease severity.MethodsPlasma Nfl and t-tau were measured in healthy controls (HC, n = 70), non-neurodegenerative neurological disease with (NND-Dem, n = 17) and without dementia syndrome (NND, n = 26), Alzheimer's disease (AD, n = 44), Creutzfeldt-Jakob disease (CJD, n = 83), dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD, n = 35), frontotemporal dementia (FTD, n = 12), and vascular dementia (VaD, n = 22). Biomarker diagnostic accuracies and cutoff points for the diagnosis of CJD were calculated, and associations between Nfl and t-tau concentrations with other fluid biomarkers, demographic, genetic, and clinical data in CJD cases were assessed. Additionally, the value of Nfl and t-tau predicting disease survival in CJD was evaluated.ResultsAmong diagnostic groups, highest plasma Nfl and t-tau concentrations were detected in CJD (fold changes of 38 and 18, respectively, compared to HC). Elevated t-tau was able to differentiate CJD from all other groups, whereas elevated Nfl concentrations were also detected in NND-Dem, AD, DLB/PDD, FTD, and VaD compared to HC. Both biomarkers discriminated CJD from non-CJD dementias with an AUC of 0.93. In CJD, plasma t-tau, but not Nfl, was associated with PRNP codon 129 genotype and CJD subtype. Positive correlations were observed between plasma Nfl and t-tau concentrations, as well as between plasma and CSF concentrations of both biomarkers (p < 0.001). Nfl was increased in rapidly progressive AD (rpAD) compared to slow progressive AD (spAD) and associated to Mini-Mental State Examination results. However, Nfl displayed higher accuracy than t-tau discriminating CJD from rpAD and spAD. Finally, plasma t-tau, but not plasma Nfl, was significantly associated with disease duration, offering a moderate survival prediction capacity.ConclusionsPlasma Nfl and t-tau are useful complementary biomarkers for the differential diagnosis of CJD. Additionally, plasma t-tau emerges as a potential prognostic marker of disease duration.

Dataset Information

Plasma p-tau₁₈₁ shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.

Introduction

Methods

Results

Discussion

Publications

Plasma p-tau<sub>181</sub> shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Plasma p-tau181 shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.

Introduction

Methods

Results

Discussion

Publications

Plasma p-tau<sub>181</sub> shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Plasma p-tau₁₈₁ shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.