Plasma P‐tau181 to Aβ42 ratio is associated with brain amyloid burden and hippocampal atrophy in an Asian cohort of Alzheimer's disease patients with concomitant cerebrovascular disease

Chong, Jenny; Ashton, Nicholas J.; Karikari, Thomas K.; Tanaka, Tomotaka; Saridin, Francis; Reilhac, Anthonin; Robins, Edward G.; Nai, Ying-Hwey; Vrooman, Henri A.; Hilal, Saima; Zetterberg, Henrik; Blennow, Kaj; Lai, Mitchell K.P.; Chen, Christopher

doi:10.1002/alz.12332

Cited by 42 publications

(70 citation statements)

References 56 publications

(106 reference statements)

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“…Several studies indicate the potential for the plasma levels of different amyloid-β (Aβ) variants to function as AD biomarkers, due to their accuracy and predictivity [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. This is not surprising considering that CSF Aβ peptides represent one of the core biomarkers in AD diagnosis, and that, at the same time, there is an urgent need to identify more accessible ones [ 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Varesi

Carrara

Pires

et al. 2022

Cells

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disease characterized by amyloid-β (Aβ) plaque deposition and neurofibrillary tangle accumulation in the brain. Although several studies have been conducted to unravel the complex and interconnected pathophysiology of AD, clinical trial failure rates have been high, and no disease-modifying therapies are presently available. Fluid biomarker discovery for AD is a rapidly expanding field of research aimed at anticipating disease diagnosis and following disease progression over time. Currently, Aβ1–42, phosphorylated tau, and total tau levels in the cerebrospinal fluid are the best-studied fluid biomarkers for AD, but the need for novel, cheap, less-invasive, easily detectable, and more-accessible markers has recently led to the search for new blood-based molecules. However, despite considerable research activity, a comprehensive and up-to-date overview of the main blood-based biomarker candidates is still lacking. In this narrative review, we discuss the role of proteins, lipids, metabolites, oxidative-stress-related molecules, and cytokines as possible disease biomarkers. Furthermore, we highlight the potential of the emerging miRNAs and long non-coding RNAs (lncRNAs) as diagnostic tools, and we briefly present the role of vitamins and gut-microbiome-related molecules as novel candidates for AD detection and monitoring, thus offering new insights into the diagnosis and progression of this devastating disease.

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Section: Resultsmentioning

confidence: 99%

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Varesi

Carrara

Pires

et al. 2022

Cells

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“…Analyses incorporating p-tau181 improved significantly, although mildly, to the addition of covariates, possibly related to the age-dependent accumulation that CSF tau is known to display [35]. To our knowledge, only one other study investigated the ratio of p-tau181/Aβ 1-42 in plasma in relation to Aβ-PET which produced an AUC of 0.89 in both CN and MCI participants [19]. The current work, conducted in in a larger cohort and in a different ethnic group, supports the utility of this measurement approach.…”

Section: Discussionmentioning

confidence: 99%

“…For example plasma Aβ1-42 and the Aβ1-42/1-40 ratio predict brain Aβ burden, and tau measured at different phosphorylation sites (threonine181 (p-tau181), threonine217 (p-tau217), threonine231 (p-tau231)) shows concordance with CSF p-tau levels (concordance ~0.8) and can predict Aβ-PET burden (AUC values ranging from 0.8 through 0.9) [9][10][11][12][13][14]. Clinical-pathological models show that understanding about the presence and severity of AD is improved when markers of amyloid and tau levels are considered simultaneously [15][16][17][18], however, to date, only one small study has investigated how combinations of plasma levels of Aβ and p-tau relate to Aβ-PET burden [19]. The first aim of this study was to investigate whether two different plasma p-tau markers (p-tau181 and p-tau231), incorporated into a ratio with Aβ, can improve predictions of Aβ burden over single analytes in comparison to PET or CSF sampling.…”

Section: Introductionmentioning

confidence: 99%

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline

Fowler

Stoops²,

Rainey‐Smith

et al. 2022

Preprint

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Background: In Alzheimer′s disease, plasma Aβ1–42 and p–tau predict high amyloid status from Aβ–PET, however the extent to which combination of both plasma assays predict remains unknown. Methods: Prototype Simoa assays were used to measure plasma samples from cognitively normal (CN) and symptomatic adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Results: The p–tau181/Aβ1–42 ratio showed the best prediction of Aβ–PET across all participants (AUC=0.905, 95%CI:0.86–0.95) and in CN (AUC=0.873; 0.80–0.94), and symptomatic (AUC=0.908; 0.82–1.00) adults. Plasma p–tau181/Aβ1–42 ratio correlated with CSF–p–tau181 (Elecsys®, Spearman′s ρ=0.74, P<0.0001) and predicted abnormal CSF Aβ (AUC=0.816, 0.74–0.89). The p-tau181/Aβ1–42 ratio also predicted future rates of cognitive decline assessed by AIBL PACC or CDR–SOB (P<0.0001). Discussion: Plasma p–tau181/Aβ1–42 ratio predicted both Aβ–PET status and cognitive decline, demonstrating potential as both a diagnostic aid and as a screening and prognostic assay for preclinical Alzheimer′s disease trials.

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“…The blood was centrifuged, aliquoted, and stored at −80 • C until use. All biomarkers were measured on the Single Molecular Array (Simoa) HD-1 Analyzer platform (Quanterix, Billerica, MA, United States) according to the manufacturer's instructions (Chong et al, 2021). The AT270 mouse monoclonal antibody specific for the threonine-181 phosphorylation site was used to measure the concentration of plasma phosphorylated P-tau181 based on an ultrasensitive Simoa immunoassay.…”

Section: Blood Biomarker Measurementsmentioning

confidence: 99%

Correlation Between Urine Formaldehyde and Cognitive Abilities in the Clinical Spectrum of Alzheimer’s Disease

Wang

Pan

Xie

et al. 2022

Front. Aging Neurosci.

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Urine-based formaldehyde has been reported to be a potential biomarker for Alzheimer’s disease (AD). However, there is a lack of research about the correlation between urine formaldehyde and cognitive abilities in the clinical spectrum of AD, especially the preclinical period. The relationship of urine formaldehyde with APOE genotype, brain Aβ status and plasma pathological markers in AD are also not clear. This study intends to explore the correlation between urine formaldehyde and cognitive abilities throughout the AD continuum, to evaluate the role of APOE genotype and Aβ accumulation on urine formaldehyde, and further to clarify the relationship between urine formaldehyde level and AD plasma pathological markers. We recruited 72 cognitively normal controls (NC), 110 subjective cognitive decline (SCD), 140 objectively defined subtle cognitive decline (Obj-SCD), 171 mild cognitive impairment (MCI) and 136 AD dementia participants. Next, we collected the data of clinical materials, neuropsychological examination, APOE genotyping, urine formaldehyde concentration, 18F-florbetapir PET imaging and plasma biomarkers. Compared with NC, Obj-SCD and MCI groups, the level of urine formaldehyde was found to be significantly upregulated in SCD group. In addition, the level of urine formaldehyde was significantly higher in AD group compared to both NC and MCI groups. Further subgroup analysis showed that, the level of urine formaldehyde was higher in APOE ε4+ subgroup compared to APOE ε4– subgroup in both NC and AD groups. There was no difference in urine formaldehyde level between the brain Aβ+ subgroup and Aβ– subgroup in each group. In addition, regression analysis showed urine formaldehyde level was correlated with gender, plasma Aβ42 and p-Tau181/T-tau. The dynamic change of urine formaldehyde in the AD continuum could be used as a potential biomarker, and combined with comprehensive cognitive evaluation could become a useful method to distinguish SCD from NC and Obj-SCD, and to distinguish MCI from AD.

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Plasma P‐tau181 to Aβ42 ratio is associated with brain amyloid burden and hippocampal atrophy in an Asian cohort of Alzheimer's disease patients with concomitant cerebrovascular disease

Cited by 42 publications

References 56 publications

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline

Correlation Between Urine Formaldehyde and Cognitive Abilities in the Clinical Spectrum of Alzheimer’s Disease

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Plasma P‐tau181 to Aβ42 ratio is associated with brain amyloid burden and hippocampal atrophy in an Asian cohort of Alzheimer's disease patients with concomitant cerebrovascular disease

Cited by 42 publications

References 56 publications

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Plasma p-tau181/Aβ1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ1-42and future cognitive decline

Correlation Between Urine Formaldehyde and Cognitive Abilities in the Clinical Spectrum of Alzheimer’s Disease

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Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline