Pathogenic <i>cis</i> p-tau levels in CSF reflects severity of traumatic brain injury

Sisakht, Alireza Mohsenian; Karamzade-Ziarati, Najme; Jahanbakhshi, Amin; Shahpasand, Koorosh; Aghababaei, Samareh; Ahmadvand, Omid; Azar, Maziar; Fattahi, Arash; Zamanzadeh, Selva

doi:10.1080/01616412.2021.2022921

Cited by 12 publications

(6 citation statements)

References 41 publications

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“…Intriguingly, both AD and CTE exhibit a similar tau isoform profile and phosphorylation state. This similarity has been observed in individuals with AD and boxers diagnosed with CTE, suggesting they might have similar pathogenic mechanisms [146,147].…”

Section: Pnt001supporting

confidence: 72%

Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies

Davidson,

Krider,

Borsellino

et al. 2023

CIMB

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Neuroinflammation, a core pathological feature observed in several neurodegenerative diseases, including Alzheimer’s disease (AD), is rapidly gaining attention as a target in understanding the molecular underpinnings of these disorders. Glial cells, endothelial cells, peripheral immune cells, and astrocytes produce a variety of pro-inflammatory mediators that exacerbate the disease progression. Additionally, microglial cells play a complex role in AD, facilitating the clearance of pathological amyloid-beta peptide (Aβ) plaques and aggregates of the tau protein. Tau proteins, traditionally associated with microtubule stabilization, have come under intense scrutiny for their perturbed roles in neurodegenerative conditions. In this narrative review, we focus on recent advances from molecular insights that have revealed aberrant tau post-translational modifications, such as phosphorylation and acetylation, serving as pathological hallmarks. These modifications also trigger the activation of CNS-resident immune cells, such as microglia and astrocytes substantially contributing to neuroinflammation. This intricate relationship between tau pathologies and neuroinflammation fosters a cascading impact on neural pathophysiology. Furthermore, understanding the molecular mechanisms underpinning tau’s influence on neuroinflammation presents a frontier for the development of innovative immunotherapies. Neurodegenerative diseases have been relatively intractable to conventional pharmacology using small molecules. We further comprehensively document the many alternative approaches using immunotherapy targeting tau pathological epitopes and structures with a wide array of antibodies. Clinical trials are discussed using these therapeutic approaches, which have both promising and disappointing outcomes. Future directions for tau immunotherapies may include combining treatments with Aβ immunotherapy, which may result in more significant clinical outcomes for neurodegenerative diseases.

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Section: Pnt001supporting

confidence: 72%

Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies

Davidson,

Krider,

Borsellino

et al. 2023

CIMB

View full text Add to dashboard Cite

show abstract

“…Immune reactions are mainly used to detect β-amyloid deposits, the Tau protein, ubiquitin and neurofilaments [ 154 , 155 ]. The detection of β-amyloid deposits is also particularly important from the perspective of the diagnosis of neuroinflammation [ 156 ].…”

Section: Diagnostics Of the Inflammatory Process In Admentioning

confidence: 99%

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Twarowski

Herbet

2023

IJMS

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Alzheimer’s disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer’s disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer’s disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.

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“…The concept that tau pathology is linked to mitochondrial dysregulation has been endorsed by studies from the field of Alzheimer’s research [ 110 , 111 , 112 , 113 ]. Kondo et al’s findings and the possible use of a p-tau therapeutic antibody were subsequently supported by a number of recent studies [ 114 , 115 , 116 ]. One study of note demonstrated a statistically significant negative correlation between Glasgow Coma Scale results and cis p-tau levels in the CSF of human TBI patients [ 117 ].…”

Section: Emerging Treatmentsmentioning

confidence: 86%

Secondary Mechanisms of Neurotrauma: A Closer Look at the Evidence

et al. 2022

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Traumatic central nervous system injury is a leading cause of neurological injury worldwide. While initial neuroresuscitative efforts are focused on ameliorating the effects of primary injury through patient stabilization, secondary injury in neurotrauma is a potential cause of cell death, oxidative stress, and neuroinflammation. These secondary injuries lack defined therapy. The major causes of secondary injury in neurotrauma include endoplasmic reticular stress, mitochondrial dysfunction, and the buildup of reactive oxygen or nitrogenous species. Stress to the endoplasmic reticulum in neurotrauma results in the overactivation of the unfolded protein response with subsequent cell apoptosis. Mitochondrial dysfunction can lead to the release of caspases and the buildup of reactive oxygen species; several characteristics make the central nervous system particularly susceptible to oxidative damage. Together, endoplasmic reticulum, mitochondrial, and oxidative stress can have detrimental consequences, beginning moments and lasting days to months after the primary injury. Understanding these causative pathways has led to the proposal of various potential treatment options.

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Pathogenic cis p-tau levels in CSF reflects severity of traumatic brain injury

Cited by 12 publications

References 41 publications

Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies

Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Secondary Mechanisms of Neurotrauma: A Closer Look at the Evidence

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