Tau Platelets Correlate with Regional Brain Atrophy in Patients with Alzheimer’s Disease

Slachevsky, Andrea; Guzmán‐Martínez, Leonardo; Delgado, Carolina; Reyes, Pablo; Farías, Gonzalo; Muñoz-Neira, Carlos; Bravo, Eduardo; Farías, Mauricio; Flores, Patricia; Garrido, Cristián; Becker, James T.; López, Oscar L.; Maccioni, Ricardo B.

doi:10.3233/jad-160652

Cited by 25 publications

(17 citation statements)

References 48 publications

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“…Owing to different catabolic cleavage, the tau fragments present in CSF and plasma will likely differ and smaller or different fragments in plasma may remain undetected by the same immunoassay that detects CSF fragments. The presence in blood of tau derived from other sources different from brain cells could also explain the lack of correlation with CSF [10,11]. The expression of tau has been shown in platelets [10], as well as in muscle, kidney, and other tissues (https://www.proteinatlas.org/ENSG00000186868‐MAPT/tissue), expanding the pool of plasma tau to additional sources compared with those for CSF tau.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, novel technologies, such as single-molecule array (SIMOA), have enabled the detection of tau at very low concentrations (picomolar) in the blood [9] . Although plasma and CSF tau are not biomarkers specific for AD as CSF P-tau and blood tau has the potential to derive from other sources in addition to neuronal tau [10] , [11] , work with ultrasensitive detection equipment suggests the potential for plasma tau to serve as a biomarker for neurodegeneration in AD as well as other neurological disorders associated with brain trauma and tauopathies [9] , [12] , [13] , [14] , [15] , [16] . Using the SIMOA technology, several studies showed higher plasma tau levels in patients with neurological disorders compared to cognitively normal (NL) controls [9] , [15] , [17] , [18] .…”

Section: Introductionmentioning

confidence: 99%

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Plasma tau complements CSF tau and P‐tau in the diagnosis of Alzheimer's disease

Fossati

Ramos‐Cejudo

Debure

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Plasma tau may be an accessible biomarker for Alzheimer's disease (AD), but the correlation between plasma and cerebrospinal fluid (CSF) tau and the value of combining plasma tau with CSF tau and phospho-tau (P-tau) are still unclear. Methods Plasma-tau, CSF-tau, and P-tau were measured in 97 subjects, including elderly cognitively normal controls (n = 68) and patients with AD (n = 29) recruited at the NYU Center for Brain Health, with comprehensive neuropsychological and magnetic resonance imaging evaluations. Results Plasma tau was higher in patients with AD than cognitively normal controls ( P < .001, area under the receiver operating characteristic curve = 0.79) similarly to CSF tau and CSF P-tau and was negatively correlated with cognition in AD. Plasma and CSF tau measures were poorly correlated. Adding plasma tau to CSF tau or CSF P-tau significantly increased the areas under the receiver operating characteristic curve from 0.80 and 0.82 to 0.87 and 0.88, respectively. Discussion Plasma tau is higher in AD independently from CSF-tau. Importantly, adding plasma tau to CSF tau or P-tau improves diagnostic accuracy, suggesting that plasma tau may represent a useful biomarker for AD, especially when added to CSF tau measures.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma tau complements CSF tau and P‐tau in the diagnosis of Alzheimer's disease

Fossati

Ramos‐Cejudo

Debure

et al. 2019

Alz & Dem Diag Ass & Dis Mo

View full text Add to dashboard Cite

show abstract

“…Blood-based p-tau has also been measured in a few recent studies and found to be elevated in AD patients [ 329 , 358 , 395 ] and MCI subjects [ 329 , 395 ] compared with controls. In addition, platelet-derived tau has been explored, and preliminary studies suggest that the ratio of high molecular weight to low molecular weight tau is higher in AD than in controls [ 264 , 337 ]. However, the role of platelet-derived tau is not clear; it could either be a confounder or help to clarify the relationship between central and peripheral compartment tau measurements.…”

Section: Tau Pathologymentioning

confidence: 99%

Current state of Alzheimer’s fluid biomarkers

et al. 2018

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

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“…Hence, blood-based biomarkers represent next-generation diagnostics for AD and other CNS diseases. One matter of concern is that blood tau has the potential to derive from other sources in addition to neuronal tau [242,243]. In this respect, novel ultrasensitive detection technologies have been developed to facilitate the detection of very low concentrations and variations of tau in the blood [186,244,245] using very high dilutions of the biological fluid: employing these technologies has pushed forward the potential for plasma tau to serve as a biomarker for neurodegeneration in AD, avoiding the interference of non-neuronal tau.…”

Section: Taumentioning

confidence: 99%

Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use

d’Abramo

D’Adamio

Giliberto

2020

JPM

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Alzheimer’s disease (AD) is the most common type of dementia, affecting more than 5 million Americans, with steadily increasing mortality and incredible socio-economic burden. Not only have therapeutic efforts so far failed to reach significant efficacy, but the real pathogenesis of the disease is still obscure. The current theories are based on pathological findings of amyloid plaques and tau neurofibrillary tangles that accumulate in the brain parenchyma of affected patients. These findings have defined, together with the extensive neurodegeneration, the diagnostic criteria of the disease. The ability to detect changes in the levels of amyloid and tau in cerebrospinal fluid (CSF) first, and more recently in blood, has allowed us to use these biomarkers for the specific in-vivo diagnosis of AD in humans. Furthermore, other pathological elements of AD, such as the loss of neurons, inflammation and metabolic derangement, have translated to the definition of other CSF and blood biomarkers, which are not specific of the disease but, when combined with amyloid and tau, correlate with the progression from mild cognitive impairment to AD dementia, or identify patients who will develop AD pathology. In this review, we discuss the role of current and hypothetical biomarkers of Alzheimer’s disease, their specificity, and the caveats of current high-sensitivity platforms for their peripheral detection.

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Tau Platelets Correlate with Regional Brain Atrophy in Patients with Alzheimer’s Disease

Cited by 25 publications

References 48 publications

Plasma tau complements CSF tau and P‐tau in the diagnosis of Alzheimer's disease

Plasma tau complements CSF tau and P‐tau in the diagnosis of Alzheimer's disease

Current state of Alzheimer’s fluid biomarkers

Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use

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