Argyrophilic grain disease: An underestimated tauopathy

Rodriguez, Roberta Diehl; Grinberg, Lea T.

doi:10.1590/s1980-57642015dn91000002

Cited by 54 publications

(36 citation statements)

References 80 publications

(143 reference statements)

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“…Only proaggregant Tau transgenic slices reveal Taupositive beaded structures in the neuropil oriented mostly perpendicular to the apical dendrites of the CA1 pyramidal cells ( Fig. 1 C and D, arrowheads) resembling grains in human AGD (16). This suggests that proaggregant Tau accumulates in the axons as grains.…”

Section: High Aggregation Propensity Is Not Necessary For Tau Missortmentioning

confidence: 91%

Adenosine A ₁ receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

Dennissen

Anglada-Huguet

Sydow

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Accumulation of Tau is a characteristic hallmark of several neurodegenerative diseases but the mode of toxic action of Tau is poorly understood. Here, we show that the Tau protein is toxic due to its aggregation propensity, whereas phosphorylation and/or missorting is not sufficient to cause neuronal dysfunction. Aggregate-prone Tau accumulates, when expressed in vitro at near-endogenous levels, in axons as spindle-shaped grains. These axonal grains contain Tau that is folded in a pathological (MC-1) conformation. Proaggregant Tau induces a reduction of neuronal ATP, concomitant with loss of dendritic spines. Counterintuitively, axonal grains of Tau are not targeted for degradation and do not induce a molecular stress response. Proaggregant Tau causes neuronal and astrocytic hypoactivity and presynaptic dysfunction instead. Here, we show that the adenosine A 1 receptor antagonist rolofylline (KW-3902) is alleviating the presynaptic dysfunction and restores neuronal activity as well as dendritic spine levels in vitro. Oral administration of rolofylline for 2-wk to 14-mo-old proaggregant Tau transgenic mice restores the spatial memory deficits and normalizes the basic synaptic transmission. These findings make rolofylline an interesting candidate to combat the hypometabolism and neuronal dysfunction associated with Tau-induced neurodegenerative diseases.tauopathies | rolofylline | hypoactivity | axons | treatment

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Section: High Aggregation Propensity Is Not Necessary For Tau Missortmentioning

confidence: 91%

Adenosine A ₁ receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

Dennissen

Anglada-Huguet

Sydow

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The brain samples used in this study contained a broad burden of AD-type pathology and were selected to be free from non-AD pathology including Lewy body disease, TDP-43 proteinopathies, primary tauopathies, and cerebrovascular changes. Argyrophilic grain disease (AGD) was not an exclusion criterion based on its high prevalence and lack of correlation with significant clinical symptoms [69][70][71] . In total, the cohort included 10 cases who underwent snRNAseq, representing Braak stages 0, 2 and 6, all ApoE 3/3, and 26 cases who underwent neuroanatomical analysis, representing Braak stages 0-6 3, 25 , ranging from 2-5 individuals per Braak stage.…”

Section: Online Methods Post-mortem Cohortmentioning

confidence: 99%

Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease

Leng

Eser

et al. 2020

Preprint

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Alzheimer's disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus -brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively -from individuals spanning the neuropathological progression of AD. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience. MAIN TEXTSelective vulnerability is a fundamental feature of neurodegenerative diseases, in which different neuronal populations show a gradient of susceptibility to degeneration 1, 2 . Selective vulnerability at the network level has been extensively explored in Alzheimer's disease (AD) 3-5 , currently the leading cause of dementia and lacking in effective therapies. However, little is known about the mechanisms underlying selective vulnerability at the cellular level in AD, which could provide insight into disease mechanisms and lead to therapeutic strategies.The entorhinal cortex (EC), an allocortex, is one of the first cortical brain regions to exhibit neuronal loss in AD 6 . Neurons in the external EC layers, especially in layer II (also known as alpha clusters of the lamina principalis externa, abbreviated "Pre-alpha") 7 , accumulate taupositive neurofibrillary changes and die early on in the course of AD 8-13 . However, these selectively vulnerable neurons have yet to be characterized extensively at the molecular level. Furthermore, it is unknown whether there are differences in vulnerability among subpopulations of these neurons. Although rodent models of AD have offered some insights [14][15][16] , the human brain has unique features with regard to cellular physiology, composition and aging [17][18][19] , limiting the extrapoloation of findings from animal models to address selective vulnerability.Previous studies have combined laser capture microdissection with microarray analysis of gene expression 20, 21 to characterize EC neurons in AD, but focused on disease-related changes in gene expression, rather than selective vulnerability. More recently, single-nucleus RNA-sequencing (snRNA-seq) has enabled large-scale characterization of transcriptomic profiles of individual cells from post-mortem human brain tissue 22, 23 . However, snRNA-seq studies of AD p...

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“…While AGD is commonly seen in the context of MCI and aging, it is very commonly comorbid with other neurodegenerative diseases, and identifying a distinctive clinical correlate has been challenging. 112,113 One understudied aspect of CTE is the dot-like lesion. 114 These lesions are common in CTE and track the other thread and tau pathology in CTE.…”

Section: Argyrophilic Grain Diseasementioning

confidence: 99%

Chronic Traumatic Encephalopathy and Neuropathological Comorbidities

Stein

Crary

2020

Semin Neurol

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AbstractWith age, the presence of multiple neuropathologies in a single individual becomes increasingly common. Given that traumatic brain injury and the repetitive head impacts (RHIs) that occur in contact sports have been associated with the development of many neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), Alzheimer's disease, Lewy body disease, and amyotrophic lateral sclerosis, it is becoming critical to understand the relationship and interactions between these pathologies. In fact, comorbid pathology is common in CTE and likely influenced by both age and the severity and type of exposure to RHI as well as underlying genetic predisposition. Here, we review the major comorbid pathologies seen with CTE and in former contact sports athletes and discuss what is known about the associations between RHI, age, and the development of neuropathologies. In addition, we examine the distinction between CTE and age-related pathology including primary age-related tauopathy and age-related tau astrogliopathy.

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Argyrophilic grain disease: An underestimated tauopathy

Cited by 54 publications

References 80 publications

Adenosine A ₁ receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

Adenosine A ₁ receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease

Chronic Traumatic Encephalopathy and Neuropathological Comorbidities

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Argyrophilic grain disease: An underestimated tauopathy

Cited by 54 publications

References 80 publications

Adenosine A 1 receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

Adenosine A 1 receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease

Chronic Traumatic Encephalopathy and Neuropathological Comorbidities

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Product

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Adenosine A ₁ receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

Adenosine A ₁ receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280