scholarly journals Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study

2021 ◽  
Vol 20 (9) ◽  
pp. 739-752 ◽  
Author(s):  
Elisabeth H Thijssen ◽  
Renaud La Joie ◽  
Amelia Strom ◽  
Corrina Fonseca ◽  
Leonardo Iaccarino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Diagnostic Performance ◽  
Phosphorylated Tau ◽  
Performance Study ◽  
Phosphorylated Tau 181

Development of a biosensor for Phosphorylated Tau 181 Protein detection in Early-Stage Alzheimer’s Disease

2022 ◽  
pp. 108057
Author(s):  
Maria Eduarda Schneider ◽  
Lucía Guillade ◽  
Miguel A. Correa-Duarte ◽  
Felismina T.C. Moreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Protein Detection ◽  
Phosphorylated Tau ◽  
Phosphorylated Tau 181

scholarly journals Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease: a systematic review and meta-analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xulong Ding ◽  
Shuting Zhang ◽  
Lijun Jiang ◽  
Lu Wang ◽  
Tao Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Operating Characteristic ◽  
Meta Analysis ◽  
Tau Proteins ◽  
Phosphorylated Tau ◽  
Diagnosis And Prognosis ◽  
Recent Advancement ◽  
Protein Assays ◽  
Phosphorylated Tau 181

AbstractA lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer’s disease (AD). Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma. Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181 (ptau181) using four ultrasensitive methods. Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls, and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic. Therefore, plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.

scholarly journals Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shi-Dong Chen ◽  
Yu-Yuan Huang ◽  
Xue-Ning Shen ◽  
Yu Guo ◽  
Lan Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Ventricular Volume ◽  
Phosphorylated Tau ◽  
Positron Emission ◽  
Amyloid Accumulation ◽  
Noninvasive Biomarker ◽  
Longitudinal Plasma ◽  
Phosphorylated Tau 181

AbstractTo assess plasma phosphorylated tau181 (p-tau181) as a progression biomarker in Alzheimer’s disease (AD), we examined longitudinal plasma p-tau181 of 1184 participants (403 cognitively normal (CN), 560 patients with mild cognitive impairment (MCI), and 221 with AD dementia) from Alzheimer’s Disease Neuroimaging Initiative (ADNI). The plasma p-tau level was increased at baseline for MCI and AD dementia (mean: CN, 15.4 pg/mL; MCI, 18.4 pg/mL; AD dementia, 23.7 pg/mL; P < 0.001) and increased significantly over time at preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stage of AD. A longitudinal increase of plasma p-tau181 was associated with abnormal cerebrospinal fluid biomarker levels (low Aβ42, high phosphorylated tau, and high total tau, all P < 0.001), amyloid accumulation (P < 0.001) and hypometabolism (P = 0.002) on positron emission tomography, atrophy in structure imaging (small hippocampal (P = 0.030), middle temporal (P = 0.008), and whole brain (P = 0.027) volume, and large ventricular volume (P = 0.008)), and deteriorated cognitive performance (global cognition and memory, language, executive function, and visuospatial function, all P < 0.050) at baseline. Furthermore, longitudinal plasma p-tau181 correlated with concurrent changes of nearly all these AD-related hallmarks and faster increase in plasma p-tau181 correlated with faster worsening cognition in all diagnostic groups. Importantly, most associations remained significant in Aβ-positive group and became non-significant in Aβ-negative group. Longitudinal analyses of plasma p-tau181 suggest its potential as a noninvasive biomarker to track disease progression in AD and to monitor effects of disease-modifying therapeutics in clinical trials.

scholarly journals ATN status in amnestic and non-amnestic Alzheimer’s disease and frontotemporal lobar degeneration

2019 ◽  
Author(s):  
Katheryn A.Q. Cousins ◽  
David J. Irwin ◽  
David A. Wolk ◽  
Edward B. Lee ◽  
Leslie M.J. Shaw ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Lobar Degeneration ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Operating Characteristic Curve

AbstractUnder the ATN framework, cerebrospinal fluid analytes provide evidence of the presence or absence of Alzheimer’s disease pathological hallmarks: amyloid plaques (A), phosphorylated tau (T), and accompanying neurodegeneration (N). Still, differences in cerebrospinal fluid levels across amnestic and non-amnestic variants or due to co-occurring pathologies might lead to misdiagnoses. We assess the diagnostic accuracy of cerebrospinal fluid markers for amyloid, tau, and neurodegeneration in an autopsy cohort of 118 Alzheimer’s disease patients (98 amnestic; 20 non-amnestic) and 64 frontotemporal lobar degeneration patients (five amnestic; 59 non-amnestic). We calculated between-group differences in cerebrospinal fluid concentrations of amyloid-β1–42 peptide, tau protein phosphorylated at threonine 181, total tau, and the ratio of phosphorylated tau to amyloid-β1–42. Results show that non-amnestic Alzheimer’s disease patients were less likely to be correctly classified under the ATN framework using independent, published biomarker cutoffs for positivity. Amyloid-β1–42 did not differ between amnestic and non-amnestic Alzheimer’s disease, and receiver operating characteristic curve analyses indicated that amyloid-β1–42 was equally effective in discriminating both groups from frontotemporal lobar degeneration. However, cerebrospinal fluid concentrations of phosphorylated tau, total tau, and the ratio of phosphorylated tau to amyloid-β1–42 were significantly lower in non-amnestic compared to amnestic Alzheimer’s disease patients. Receiver operating characteristic curve analyses for these markers showed reduced area under the curve when discriminating non-amnestic Alzheimer’s disease from frontotemporal lobar degeneration, compared to discrimination of amnestic Alzheimer’s disease from frontotemporal lobar degeneration. In addition, the ATN framework was relatively insensitive to frontotemporal lobar degeneration, and these patients were likely to be classified as having normal biomarkers or biomarkers suggestive of primary Alzheimer’s disease pathology. We conclude that amyloid-β1–42 maintains high sensitivity to A status, although with lower specificity, and this single biomarker provides better sensitivity to non-amnestic Alzheimer’s disease than either the ATN framework or the phosphorylated-tau/amyloid-β1–42 ratio. In contrast, T and N status biomarkers differed between amnestic and non-amnestic Alzheimer’s disease; standard cutoffs for phosphorylated tau and total tau may thus result in misclassifications for non-amnestic Alzheimer’s patients. Consideration of clinical syndrome may help improve the accuracy of ATN designations for identifying true non-amnestic Alzheimer’s disease.Abbreviated SummaryCousins et al. assess the 2018 ATN framework and find that non-amnestic patients with Alzheimer’s disease (AD) have lower cerebrospinal fluid (CSF) phosphorylated tau and total tau than amnestic AD, while CSF amyloid-β accurately stratifies both non-amnestic and amnestic AD from frontotemporal lobar degeneration.

scholarly journals ATN status in amnestic and non-amnestic Alzheimer’s disease and frontotemporal lobar degeneration

Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2295-2311 ◽  
Author(s):  
Katheryn A Q Cousins ◽  
David J Irwin ◽  
David A Wolk ◽  
Edward B Lee ◽  
Leslie M J Shaw ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Frontotemporal Lobar Degeneration ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Operating Characteristic Curve

Abstract Under the ATN framework, CSF analytes provide evidence of the presence or absence of Alzheimer’s disease pathological hallmarks: amyloid plaques (A), phosphorylated tau (T), and accompanying neurodegeneration (N). Still, differences in CSF levels across amnestic and non-amnestic variants or due to co-occurring pathologies might lead to misdiagnoses. We assess the diagnostic accuracy of CSF markers for amyloid, tau, and neurodegeneration in an autopsy cohort of 118 Alzheimer’s disease patients (98 amnestic; 20 non-amnestic) and 64 frontotemporal lobar degeneration patients (five amnestic; 59 non-amnestic). We calculated between-group differences in CSF concentrations of amyloid-β1–42 peptide, tau protein phosphorylated at threonine 181, total tau, and the ratio of phosphorylated tau to amyloid-β1–42. Results show that non-amnestic Alzheimer’s disease patients were less likely to be correctly classified under the ATN framework using independent, published biomarker cut-offs for positivity. Amyloid-β1–42 did not differ between amnestic and non-amnestic Alzheimer’s disease, and receiver operating characteristic curve analyses indicated that amyloid-β1–42 was equally effective in discriminating both groups from frontotemporal lobar degeneration. However, CSF concentrations of phosphorylated tau, total tau, and the ratio of phosphorylated tau to amyloid-β1–42 were significantly lower in non-amnestic compared to amnestic Alzheimer’s disease patients. Receiver operating characteristic curve analyses for these markers showed reduced area under the curve when discriminating non-amnestic Alzheimer’s disease from frontotemporal lobar degeneration, compared to discrimination of amnestic Alzheimer’s disease from frontotemporal lobar degeneration. In addition, the ATN framework was relatively insensitive to frontotemporal lobar degeneration, and these patients were likely to be classified as having normal biomarkers or biomarkers suggestive of primary Alzheimer’s disease pathology. We conclude that amyloid-β1–42 maintains high sensitivity to A status, although with lower specificity, and this single biomarker provides better sensitivity to non-amnestic Alzheimer’s disease than either the ATN framework or the phosphorylated-tau/amyloid-β1–42 ratio. In contrast, T and N status biomarkers differed between amnestic and non-amnestic Alzheimer’s disease; standard cut-offs for phosphorylated tau and total tau may thus result in misclassifications for non-amnestic Alzheimer’s disease patients. Consideration of clinical syndrome may help improve the accuracy of ATN designations for identifying true non-amnestic Alzheimer’s disease.

scholarly journals Assessment of cerebral microbleeds by susceptibility-weighted imaging in Alzheimer’s disease patients: A neuroimaging biomarker of the disease

2017 ◽  
Vol 30 (4) ◽  
pp. 330-335 ◽  
Author(s):  
Gianvincenzo Sparacia ◽  
Francesco Agnello ◽  
Giuseppe La Tona ◽  
Alberto Iaia ◽  
Federico Midiri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Amyloid Beta ◽  
Cerebral Microbleeds ◽  
Susceptibility Weighted Imaging ◽  
Phosphorylated Tau ◽  
Protein Levels ◽  
Phosphorylated Tau 181

Purpose The objective of this study was to correlate the presence and distribution of cerebral microbleeds in Alzheimer’s disease patients with cerebrospinal fluid biomarkers (amyloid-beta and phosphorylated tau 181 protein levels) and cognitive decline by using susceptibility-weighted imaging magnetic resonance sequences at 1.5 T. Material and methods Fifty-four consecutive Alzheimer’s disease patients underwent brain magnetic resonance imaging at 1.5 T to assess the presence and distribution of cerebral microbleeds on susceptibility-weighted imaging images. The images were analyzed in consensus by two neuroradiologists, each with at least 10 years’ experience. Dementia severity was assessed with the Mini-Mental State Examination score. A multiple regression analysis was performed to assess the associations between the number and location of cerebral microbleed lesions with the age, sex, duration of the disease, cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels, and cognitive functions. Results A total of 296 microbleeds were observed in 54 patients; 38 patients (70.4%) had lobar distribution, 13 patients (24.1%) had non-lobar distribution, and the remaining three patients (5.6%) had mixed distribution, demonstrating that Alzheimer’s disease patients present mainly a lobar distribution of cerebral microbleeds. The age and the duration of the disease were correlated with the number of lobar cerebral microbleeds ( P < 0.001). Cerebrospinal fluid amyloid-beta, phosphorylated tau 181 protein levels, and cognitive decline were correlated with the number of lobar cerebral microbleeds in Alzheimer’s disease patients ( P < 0.001). Conclusion Lobar distribution of cerebral microbleeds is associated with Alzheimer’s disease and the number of lobar cerebral microbleeds directly correlates with cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels and with the cognitive decline of Alzheimer’s disease patients.

Sign in / Sign up

Export Citation Format

Share Document