Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration

González‐Ortiz, Fernándo; Turton, Michael; Kac, Przemysław R; Smirnov, Denis S.; Premi, Enrico; Ghidoni, Roberta; Benussi, Luisa; Cantoni, Valentina; Saraceno, Claudia; Rivolta, Jasmine; Ashton, Nicholas J.; Borroni, Barbara; Galasko, Douglas; Harrison, Peter; Zetterberg, Henrik; Blennow, Kaj; Karikari, Thomas K.

doi:10.1093/brain/awac407

Cited by 98 publications

(96 citation statements)

References 71 publications

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“…CSF tau fragments starting from amino acid 243 are also shown to associate with tau PET, and could thus be a marker of soluble tau aggregates [38]. Furthermore, brain-derived tau, an assay capturing central nervous system tau released into blood, demonstrates specificity to AD and might reflect neurodegeneration due to AD [39].…”

Section: Novel P-tau Biomarkers In Csfmentioning

confidence: 99%

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

González‐Ortiz

Kac

Brum

et al. 2023

Mol Neurodegeneration

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As the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, and healthcare systems. Although AD can be identified and diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence and clinical symptoms, challenges regarding practicality and accessibility hinder their widespread availability and implementation. Consequently, many people with suspected cognitive impairment due to AD do not receive a biomarker-supported diagnosis. Blood biomarkers have the capacity to help expand access to AD diagnostics worldwide. One such promising biomarker is plasma phosphorylated tau (p-tau), which has demonstrated specificity to AD versus non-AD neurodegenerative diseases, and will be extremely important to inform on clinical diagnosis and eligibility for therapies that have recently been approved. This review provides an update on the diagnostic and prognostic performances of plasma p-tau181, p-tau217 and p-tau231, and their associations with in vivo and autopsy-verified diagnosis and pathological hallmarks. Additionally, we discuss potential applications and unanswered questions of plasma p-tau for therapeutic trials, given their recent addition to the biomarker toolbox for participant screening, recruitment and during-trial monitoring. Outstanding questions include assay standardization, threshold generation and biomarker verification in diverse cohorts reflective of the wider community attending memory clinics and included in clinical trials.

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Section: Novel P-tau Biomarkers In Csfmentioning

confidence: 99%

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

González‐Ortiz

Kac

Brum

et al. 2023

Mol Neurodegeneration

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“…For example, it has been found that direct injection of glutamate into rat insula with no other intervention led to IENFD reductions, highlighting the possibility that imbalances in CNS excitatory neurotransmitters may play a role in IENFD ( 32 ). Alternatively, a “top-around” effect in which signaling molecules or factors are released due to CNS injury could secondarily impact peripheral fibers through the bloodstream or other nonneural pathways ( 33–37 ).…”

Section: Discussionmentioning

confidence: 99%

Abnormal intraepidermal nerve fiber density in disease: A scoping review

et al. 2023

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BackgroundIntraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique.MethodsWe conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5).ResultsWe analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 73 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of −47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of −31.6% and −34.7%, respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents.InterpretationReduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.

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“…For example, it has been found that direct injection of glutamate into rat insula with no other intervention led to IENFD reductions, highlighting the possibility that imbalances in CNS excitatory neurotransmitters may play a role in IENFD [31]. Alternatively, a "top-around" effect in which signaling molecules or factors are released due to CNS injury could secondarily impact peripheral fibers through the bloodstream or other nonneural pathways [32][33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

Thomas

Enders

Kaiser

et al. 2023

Preprint

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Background: Intraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique. Methods: We conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5). Results: We analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 74 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of -47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of -31.6 % and -34.7% respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents. Interpretation: Reduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.

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Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration

Cited by 98 publications

References 71 publications

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications

Abnormal intraepidermal nerve fiber density in disease: A scoping review

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review

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