Experimental evidence for the age dependence of tau protein spread in the brain

Wegmann, Susanne; Bennett, Rachel E.; Delorme, L. D.; Robbins, Ashley B.; Hu, Miwei; McKenzie, Danny; Kirk, Molly J.; Schiantarelli, Julia; Tunio, Nahel A.; Amaral, André Cestonaro do; Fan, Zhanyun; Nicholls, Samantha B.; Hudry, Eloïse; Hyman, Bradley T.

doi:10.1126/sciadv.aaw6404

Cited by 120 publications

(128 citation statements)

References 39 publications

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“…In our study, using the Drosophila in-vivo model, we demonstrate that human tau propagates trans-cellularly from the site of targeted expression to the additional regions of the adult fly brain by the factor of age. Hence, our finding is in line with the previous reports which also proclaim the migration of tau pathology in other model systems [13,14].…”

Section: Introductionsupporting

confidence: 94%

Age dependent trans-cellular propagation of human tau aggregates inDrosophiladisease models

Aqsa

Sarkar

2020

Preprint

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Tauopathies is a class of neurodegenerative disorders which involves the transformation of physiological tau into pathogenic tau. One of the prime causes reported to drive this conversion is tau hyperphosphorylation and the subsequent propagation of pathogenic protein aggregates across the nervous system. Although past attempts have been made to deduce the details of tau propagation, yet not much is known about its mechanism. A better understanding of this aspect of disease pathology can prove to be beneficial for the development of diagnostic and therapeutic approaches. In our work, we utilize the plethora of advantages procured by Drosophila to introduce a novel in-vivo tauopathy propagation model. For the first time, we demonstrate that the human tau (h-tau) possesses an intrinsic property to spread trans-cellularly in the fly nervous system irrespective of the tau allele or the neuronal tissue type. Aggregate migration restricted by targeted down-regulation of a specific kinase, elucidates the role of hyper-phosphorylation in its movement. On the contrary to the previous models, the present system enables a rapid, convenient and robust in-vivo study of tau migration pathology. Henceforth, the developed model would not only be immensely helpful in uncovering the mechanistic in-depths of tau propagation pathology but also aid in modifier and/or drug screening for amelioration of tauopathies.

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Section: Introductionsupporting

confidence: 94%

Age dependent trans-cellular propagation of human tau aggregates inDrosophiladisease models

Aqsa

Sarkar

2020

Preprint

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“…Several in vitro [ 95 ] and in vivo studies [ 96 , 97 , 98 , 99 ] have revealed that tau is transmitted from one cell to another following a stereotypical pattern, thus supporting the tau prion propagation hypothesis in AD and other tauopathies [ 100 ]. Although these observations provide solid evidence of this phenomenon, the mechanisms of tau release, internalization, and processing are still being studied.…”

Section: Tau Proteinmentioning

confidence: 91%

Microglia in Alzheimer’s Disease in the Context of Tau Pathology

2020

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Microglia are the cells that comprise the innate immune system in the brain. First described more than a century ago, these cells were initially assigned a secondary role in the central nervous system (CNS) with respect to the protagonists, neurons. However, the latest advances have revealed the complexity and importance of microglia in neurodegenerative conditions such as Alzheimer’s disease (AD), the most common form of dementia associated with aging. This pathology is characterized by the accumulation of amyloid-β peptide (Aβ), which forms senile plaques in the neocortex, as well as by the aggregation of hyperphosphorylated tau protein, a process that leads to the development of neurofibrillary tangles (NFTs). Over the past few years, efforts have been focused on studying the interaction between Aβ and microglia, together with the ability of the latter to decrease the levels of this peptide. Given that most clinical trials following this strategy have failed, current endeavors focus on deciphering the molecular mechanisms that trigger the tau-induced inflammatory response of microglia. In this review, we summarize the most recent studies on the physiological and pathological functions of tau protein and microglia. In addition, we analyze the impact of microglial AD-risk genes (APOE, TREM2, and CD33) in tau pathology, and we discuss the role of extracellular soluble tau in neuroinflammation.

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“…Tau proteins (or Tau aggregates) migrate along nerve fibers and thus contribute to the spread of the disease throughout the brain [74]. If proteins spread more quickly in the aging brain, this might explain why most people with Alzheimer's disease are older [75].…”

Section: Tau Inhibitionmentioning

confidence: 99%

Curcumin’s Nanomedicine Formulations for Therapeutic Application in Neurological Diseases

Salehi

Calina

Docea

et al. 2020

JCM

134

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The brain is the body’s control center, so when a disease affects it, the outcomes are devastating. Alzheimer’s and Parkinson’s disease, and multiple sclerosis are brain diseases that cause a large number of human deaths worldwide. Curcumin has demonstrated beneficial effects on brain health through several mechanisms such as antioxidant, amyloid β-binding, anti-inflammatory, tau inhibition, metal chelation, neurogenesis activity, and synaptogenesis promotion. The therapeutic limitation of curcumin is its bioavailability, and to address this problem, new nanoformulations are being developed. The present review aims to summarize the general bioactivity of curcumin in neurological disorders, how functional molecules are extracted, and the different types of nanoformulations available.

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Experimental evidence for the age dependence of tau protein spread in the brain

Cited by 120 publications

References 39 publications

Age dependent trans-cellular propagation of human tau aggregates inDrosophiladisease models

Age dependent trans-cellular propagation of human tau aggregates inDrosophiladisease models

Microglia in Alzheimer’s Disease in the Context of Tau Pathology

Curcumin’s Nanomedicine Formulations for Therapeutic Application in Neurological Diseases

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