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Background: Frontotemporal dementia (FTD) is a neurodegenerative disease with clinical, pathological, and genetic heterogeneity. FTD is receiving increasing attention because it is the second leading cause of early-onset dementia after Alzheimer's disease. This study aimed to analyse the research trends and hotspots of FTD from 2000 to 2022 using bibliometrics. Methods: Papers related to FTD from 2000 to 2020 were systematically searched through the Web of Science Core Collection (WOSCC). Citespace and Vosviewer software were used to visually analyse the retrieved data of countries/regions, institutions, journals, authors, references, and keywords. Microsoft Excel was used to generate the annual publications and growth trends. Results: There were 10,227 papers included in the bibliometric analysis. The annual publication output on FTD has increased significantly from 2000 to 2022, with papers published in 934 academic journals and 87 countries/regions. The Journal of Alzheimer's Disease was the most popular, with 488 papers about FTD. The most productive countries/regions, institutions, and authors are the United States (n = 4,037), the University of California San Francisco (n = 687), and Miller, Bruce L. (n = 427), respectively. The article by Katya Rascovsky and her colleagues published on Brain in 2011 was the most cocited paper, with 625 citations. The research hotspots in this field were the clinical diagnostic criteria, subdivision, and pathological mechanism of FTD, such as tau protein, chromosome 17, progranulin, TDP-43, and C9orf72. Conclusion: The future research direction is based on biomarkers and pathological mechanisms to diagnose and differential diagnose FTD from the aspects of behavior, neuropathology, neuroimaging, and serum markers. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V–H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V–H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V–H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer's disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer's disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer's disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer's disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer's disease worldwide. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disorder with a significant global impact on public health. The emergence of atypical clinical phenotypes challenges traditional diagnostic approaches, necessitating a deeper exploration of biomarkers for accurate identification. The US Food and Drug Administration (FDA) classification of biomarkers and their integration into different stages of AD provide a structured framework for their application in research and clinical settings. Within the context of AD drug development, biomarkers are essential for participant selection, target engagement evaluation, and assessment of pathological hallmarks, including Aβ and tau protein abnormalities. The incorporation of nanoparticles with a biodegradable approach introduces innovative strategies to address the complexities of AD. This paper extensively discusses biomarkers associated with synaptic dysfunction, neuroinflammation, and glial activation, recognizing their significance in elucidating disease mechanisms. Common pathologies such as synuclein and TDP‐43 further underscore the multifaceted nature of AD. Current biomarkers for AD diagnosis, encompassing cerebral spinal fluid (CSF) biomarkers and various imaging modalities, reflect the ongoing efforts to enhance early detection and monitoring. Intriguingly, novel biomarkers continue to emerge, offering promising avenues for improved understanding and intervention. Current review provides a comprehensive survey of biomarkers for AD, elucidating their diverse roles across different aspects of the disease. By highlighting their contributions to diagnosis, drug development, and mechanistic insights, this overview underscores the importance of biomarker research in the pursuit of effective AD management and treatment strategies. [ABSTRACT FROM AUTHOR]

This article provides an overview of recent research on neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, ALS, Huntington's disease, and diabetic neuropathy. The prevalence of these diseases is increasing, and current treatments only manage symptoms. The research discussed in the article focuses on understanding the underlying mechanisms of neurodegeneration and developing more effective therapies. Topics covered include blood-based diagnostic kits, potential therapeutic approaches, molecular mechanisms of specific drugs, autophagy regulation, neuroprotective effects of andrographolide, and the effects of supplements and vitamin E on the nervous system. The goal of this research is to address the growing impact of neurodegenerative diseases and improve patient outcomes. [Extracted from the article]

The most prevalent cause of dementia is Alzheimer's disease. Cognitive decline and accelerating memory loss characterize it. Alzheimer's disease advances sequentially, starting with preclinical stages, followed by mild cognitive and/or behavioral impairment, and ultimately leading to Alzheimer's disease dementia. In recent years, healthcare providers have been advised to make an earlier diagnosis of Alzheimer's, prior to individuals developing Alzheimer's disease dementia. Regrettably, the identification of early-stage Alzheimer's disease in clinical settings can be arduous due to the tendency of patients and healthcare providers to disregard symptoms as typical signs of aging. Therefore, accurate and prompt diagnosis of Alzheimer's disease is essential in order to facilitate the development of disease-modifying and secondary preventive therapies prior to the onset of symptoms. There has been a notable shift in the goal of the diagnosis process, transitioning from merely confirming the presence of symptomatic AD to recognizing the illness in its early, asymptomatic phases. Understanding the evolution of disease-modifying therapies and putting effective diagnostic and therapeutic management into practice requires an understanding of this concept. The outcomes of this study will enhance indepth knowledge of the current status of Alzheimer's disease's diagnosis and treatment, justifying the necessity for the quest for potential novel biomarkers that can contribute to determining the stage of the disease, particularly in its earliest stages. Interestingly, latest clinical trial status on pharmacological agents, the nonpharmacological treatments such as behavior modification, exercise, and cognitive training as well as alternative approach on phytochemicals as neuroprotective agents have been covered in detailed. [ABSTRACT FROM AUTHOR]

Dendrimers are covalently bonded globular nanostructures that may be used in the treatment of Alzheimer's disease (AD). Nowadays, AD therapies are focused on improving cognitive functioning and not causal treatment. However, this may change with the use of dendrimers, which are being investigated as a drug-delivery system or as a drug per se. With their ability to inhibit amyloid formation and their anti-tau properties, they are a promising therapeutic option for AD patients. Studies have shown that dendrimers may inhibit amyloid formation in at least two ways: by blocking fibril growth and by breaking already existing fibrils. Neurofibrillary tangles (NFTs) are abnormal filaments built by tau proteins that can be accumulated in the cell, which leads to the loss of cytoskeletal microtubules and tubulin-associated proteins. Cationic phosphorus dendrimers, with their anti-tau properties, can induce the aggregation of tau into amorphous structures. Drug delivery to mitochondria is difficult due to poor transport across biological barriers, such as the inner mitochondrial membrane, which is highly negatively polarized. Dendrimers may be potential nanocarriers and increase mitochondria targeting. Another considered use of dendrimers in AD treatment is as a drug-delivery system, for example, carbamazepine (CBZ) or tacrine. They can also be used to transport siRNA into neuronal tissue and to carry antioxidants and anti-inflammatory drugs to act protectively on the nervous system. [ABSTRACT FROM AUTHOR]

Background: Leveraging Alzheimer's disease (AD) imaging biomarkers and longitudinal cognitive data may allow us to establish evidence of cognitive resilience (CR) to AD pathology in-vivo. Here, we applied latent class mixture modeling, adjusting for sex, baseline age, and neuroimaging biomarkers of amyloid, tau and neurodegeneration, to a sample of cognitively unimpaired older adults to identify longitudinal trajectories of CR. Methods: We identified 200 Harvard Aging Brain Study (HABS) participants (mean age = 71.89 years, SD = 9.41 years, 59% women) who were cognitively unimpaired at baseline with 2 or more timepoints of cognitive assessment following a single amyloid-PET, tau-PET and structural MRI. We examined latent class mixture models with longitudinal cognition as the dependent variable and time from baseline, baseline age, sex, neocortical Aβ, entorhinal tau, and adjusted hippocampal volume as independent variables. We then examined group differences in CR-related factors across the identified subgroups from a favored model. Finally, we applied our favored model to a dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 160, mean age = 73.9 years, SD = 7.6 years, 60% women). Results: The favored model identified 3 latent subgroups, which we labelled as Normal (71% of HABS sample), Resilient (22.5%) and Declining (6.5%) subgroups. The Resilient subgroup exhibited higher baseline cognitive performance and a stable cognitive slope. They were differentiated from other groups by higher levels of verbal intelligence and past cognitive activity. In ADNI, this model identified a larger Normal subgroup (88.1%), a smaller Resilient subgroup (6.3%) and a Declining group (5.6%) with a lower cognitive baseline. Conclusion: These findings demonstrate the value of data-driven approaches to identify longitudinal CR groups in preclinical AD. With such an approach, we identified a CR subgroup who reflected expected characteristics based on previous literature, higher levels of verbal intelligence and past cognitive activity. [ABSTRACT FROM AUTHOR]

• Multimodal strategies and interventions, e.g. healthy lifestyle (dietary and physical activity), can be recommended for treatment of Alzheimer's disease (AD). • Gene study and gene-based therapy with a critical role in the detection and cure of AD will have a fundamental role. • Attempts to enhance clinical results are focused on several main areas including design and detection of more effective carrier molecules, selection of the best gene delivery methods, and detection of novel therapeutic targets. Neurodegenerative diseases such as Alzheimer's disease (AD) are still an important issue for scientists because it is difficult to cure with the available molecular medications and conventional treatments. Due to the complex nature of the brain structures and heterogeneous morphological and physiological properties of neuronal cells, interventions for cerebral-related disorders using surgical approaches, and classical and ongoing treatments remain hard for physicians. Furthermore, the development of newly designed medications attempts to target AD are not successful in improving AD, because abnormalities of tau protein, aggregation of amyloid β (Aβ) peptide, inflammatory responses, etc lead to advanced neurodegeneration processes that conventional treatments cannot stop them. In recent years, novel diagnostic strategies and therapeutic approaches have been developed to identify and cure early pathological events of AD. Accordingly, many gene-based therapies have been developed and introduce the therapeutic potential to prevent and cure AD. On the other hand, genetic investigations and postmortem assessments have detected a large number of factors associated with AD pathology. Also, genetically diverse animal models of AD help us to detect and prioritize novel resilience mechanisms. Hence, gene therapy can be considered an effective and powerful tool to identify and treat human diseases. Ultimately, gene study and gene-based therapy with a critical role in the detection and cure of various human disorders will have a fundamental role in our lives forever. This scientific review paper discusses the present status of different therapeutic strategies, particularly gene-based therapy in treating AD, along with its challenges. [ABSTRACT FROM AUTHOR]

The microtubule-associated protein Tau is a key player in various neurodegenerative conditions, including Alzheimer's disease (AD) and Tauopathies, where its hyperphosphorylation disrupts neuronal microtubular lattice stability. Glaucoma, a neurodegenerative disorder affecting the retina, leads to irreversible vision loss by damaging retinal ganglion cells and the optic nerve, often associated with increased intraocular pressure. Prior studies have indicated Tau expression and phosphorylation alterations in the retina in both AD and glaucoma, yet the causative or downstream nature of Tau protein changes in these pathologies remains unclear. This study investigates the impact of Tau protein modulation on retinal neurons under normal and experimental glaucoma conditions. Employing AAV9-mediated gene therapy for Tau overexpression and knockdown, both manipulations were found to adversely affect retinal structural and functional measures as well as neuroprotective Akt/Erk survival signalling in healthy conditions. In the experimental glaucoma model, Tau overexpression intensified inner retinal degeneration, while Tau silencing provided significant protection against these degenerative changes. These findings underscore the critical role of endogenous Tau protein levels in preserving retinal integrity and emphasize the therapeutic potential of targeting Tau in glaucoma pathology. [ABSTRACT FROM AUTHOR]

The spread of prion‐like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion‐like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it is shown that the lymphocyte‐activation gene 3 (Lag3) is a cell surface receptor that binds to PFF but not the monomer of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron‐to‐neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. These results identify neuronal Lag3 as a receptor of pathologic Tau in the brain，and for AD and related Tauopathies, a therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The aggregation and spread of misfolded amyloid structured proteins, such as tau and α-synuclein, are key pathological features associated with neurodegenerative disorders, including Alzheimer's and Parkinson's disease. These proteins possess a prion-like property, enabling their transmission from cell to cell leading to propagation throughout the central and peripheral nervous systems. While the mechanisms underlying their intracellular spread are still being elucidated, targeting the extracellular space has emerged as a potential therapeutic approach. The glymphatic system, a brain-wide pathway responsible for clearing extracellular metabolic waste from the central nervous system, has gained attention as a promising target for removing these toxic proteins. Methods: In this study, we investigated the impact of long-term modulation of glymphatic function on tau aggregation and spread by chronically treating a mouse model of tau propagation with a pharmacological inhibitor of AQP4, TGN-020. Thy1-hTau.P301S mice were intracerebrally inoculated with tau into the hippocampus and overlying cortex, and subsequently treated with TGN-020 (3 doses/week, 50 mg/kg TGN-020, i.p.) for 10-weeks. During this time, animal memory was studied using cognitive behavioural tasks, and structural MR images were acquired of the brain in vivo prior to brain extraction for immunohistochemical characterisation. Results: Our findings demonstrate increased tau aggregation in the brain and transhemispheric propagation in the hippocampus following the inhibition of glymphatic clearance. Moreover, disruption of the glymphatic system aggravated recognition memory in tau inoculated mice and exacerbated regional changes in brain volume detected in the model. When initiation of drug treatment was delayed for several weeks post-inoculation, the alterations were attenuated. Conclusions: These results indicate that by modulating AQP4 function and, consequently, glymphatic clearance, it is possible to modify the propagation and pathological impact of tau in the brain, particularly during the initial stages of the disease. These findings highlight the critical role of the glymphatic system in preserving healthy brain homeostasis and offer valuable insights into the therapeutic implications of targeting this system for managing neurodegenerative diseases characterized by protein aggregation and spread. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD. [ABSTRACT FROM AUTHOR]

Progressive neurocognitive dysfunction is the leading cause of a reduced quality of life in patients with primary brain tumors. Understanding how the human brain responds to cancer and its treatment is essential to improve the associated cognitive sequelae. In this study, we performed integrated transcriptomic and tissue analysis on postmortem normal‐appearing non‐tumor brain tissue from glioblastoma (GBM) patients that had received cancer treatments, region‐matched brain tissue from unaffected control individuals and Alzheimer's disease (AD) patients. We show that normal‐appearing non‐tumor brain regions of patients with GBM display hallmarks of accelerated aging, in particular mitochondrial dysfunction, inflammation, and proteostasis deregulation. The extent and spatial pattern of this response decreased with distance from the tumor. Gene set enrichment analyses and a direct comparative analysis with an independent cohort of brain tissue samples from AD patients revealed a significant overlap in differentially expressed genes and a similar biological aging trajectory. Additionally, these responses were validated at the protein level showing the presence of increased lysosomal lipofuscin, phosphorylated microtubule‐associated protein Tau, and oxidative DNA damage in normal‐appearing brain areas of GBM patients. Overall, our data show that the brain of GBM patients undergoes accelerated aging and shared AD‐like features, providing the basis for novel or repurposed therapeutic targets for managing brain tumor‐related side effects. [ABSTRACT FROM AUTHOR]

Background and purpose: Alzheimer's disease (AD) is a common neurodegenerative disease and the fifth leading cause of death among the elderly. The development of drugs for AD treatment is based on inhibiting cholinesterase (ChE) activity and inhibiting amyloid-beta peptide and tau protein aggregations. Many in vitro findings have demonstrated that thiazole- and thiazolidine-based compounds have a good inhibitory effect on ChE and other elements involved in the AD pathogenicity cascade. Experimental approach: In the present review, we collected available documents to verify whether these synthetic compounds can be a step forward in developing new medications for AD. A systematic literature search was performed in major electronic databases in April 2021. Twenty-eight relevant in vitro and in vivo studies were found and used for data extraction. Findings/Results: Findings demonstrated that thiazole- and thiazolidine-based compounds could ameliorate AD's pathologic condition by affecting various targets, including inhibition of ChE activity, amyloid-beta, and tau aggregation in addition to cyclin-dependent kinase 5/p25, beta-secretase-1, cyclooxygenase, and glycogen synthase kinase-3β. Conclusion and implications: Due to multitarget effects at micromolar concentration, this review demonstrated that these synthetic compounds could be considered promising candidates for developing anti-Alzheimer drugs. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the noninvasive collection of saliva, we designed the systematic review to answer the question "Are salivary biomarkers reliable for the diagnosis of Alzheimer's Disease?" Following the inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Potential biomarkers include mainly proteins, metabolites and even miRNAs. Based on meta-analysis, in AD patients, salivary levels of beta-amyloid42 and p-tau levels were significantly increased, and t-tau and lactoferrin were decreased at borderline statistical significance. However, according to pooled AUC, lactoferrin and beta-amyloid42 showed a significant predictive value for salivary-based AD diagnosis. In conclusion, potential markers such as beta-amyloid42, tau and lactoferrin can be detected in the saliva of AD patients, which could reliably support the early diagnosis of this neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Introduction Alzheimer's disease is a neurocognitive disorder that affects elderly people by slowly impaired cognition, dementia, and gets worse with age. It slowly impacts the quality of life. Clinically, it is distinguished by a transition from episodic memory to a gradual reduction in cognitive ability leading to cognitive dysfunction. Neurofibrillary tangles and amyloid plaques are unique structures that are thought to have a role in the pathogenesis of Alzheimer's disease. In this review, we focus our attention on the risk factors, pathophysiology, etiology, epidemiology, stages, diagnosis, treatment, mechanisms, pathways, ongoing clinical trials data and risks potentially associated with the development of Alzheimer's disease. Short summary This review aims to extrapolate the information about Alzheimer's disease. Preliminary research was done by selecting reviews on PubMed, Elsevier, and Google open-access publications using the keywords like "Alzheimer, dementia, neurodegenerative, memory, amyloid β, mechanism of action, pathways". Conclusion Here we show the discussion and interpretation of several signaling pathways in the pathogenesis of Alzheimer's disease such as amyloid β plaque cleavage, Metal ion hypothesis, amyloid β degradation, initiation of amyloidogenic and non-amyloidogenic pathway, oxidative stress hypothesis, Metabolic syndrome, insulin resistance and tau phosphorylation associated apolipoprotein- cholesterol, neurofibrillary tangles accumulation, and insulin resistance which are significant for better understanding of the disease initiation and progression. On studying the ongoing clinical trials, it was found that current drugs being tested are crenezumab, gantenerumab and sodium oligonucleotide. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an extremely devastating neurodegenerative disease, and there is no cure for it. AD is specified as the misfolding and aggregation of amyloid-β protein (Aβ) and abnormalities in hyperphosphorylated tau protein. Current approaches to treat Alzheimer's disease have had some success in slowing down the disease's progression. However, attempts to find a cure have been largely unsuccessful, most likely due to the complexity associated with AD pathogenesis. Hence, a shift in focus to better understand the molecular mechanism of Aβ processing and to consider alternative options such as chaperone proteins seems promising. Chaperone proteins act as molecular caretakers to facilitate cellular homeostasis under standard conditions. Chaperone proteins like heat shock proteins (Hsps) serve a pivotal role in correctly folding amyloid peptides, inhibiting mitochondrial dysfunction, and peptide aggregation. For instance, Hsp90 plays a significant role in maintaining cellular homeostasis through its protein folding mechanisms. In this review, we analyze the most recent studies from 2020 to 2023 and provide updates on Aβ regulation by Hsp90, BRICHOS domain chaperone, and distinctive newly reported chaperones. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. While the accumulation of Aβ is pivotal to the etiology of AD, both the microtubule-associated protein tau (MAPT) and the F-actin severing protein cofilin are necessary for the deleterious effects of Aβ. However, the molecular link between tau and cofilin remains unclear. In this study, we found that cofilin competes with tau for direct microtubule binding in vitro, in cells, and in vivo, which inhibits tau-induced microtubule assembly. Genetic reduction of cofilin mitigates tauopathy and synaptic defects in Tau-P301S mice and movement deficits in tau transgenic C. elegans. The pathogenic effects of cofilin are selectively mediated by activated cofilin, as active but not inactive cofilin selectively interacts with tubulin, destabilizes microtubules, and promotes tauopathy. These results therefore indicate that activated cofilin plays an essential intermediary role in neurotoxic signaling that promotes tauopathy. Jung-A A. Woo et al. show that activated cofilin competes with Tau for microtubule biding in primary neuronal cultures and a C.elegans model. This direct binding decreases microtubule stability and promotes tauopathy, suggesting an important role for cofilin in neurotoxic signaling. [ABSTRACT FROM AUTHOR]