Abstract：
:Accumulation of the tau protein in fibrillar intracellular aggregates is a defining feature of multiple neurodegenerative diseases collectively referred to as tauopathies. Despite intensive study of tau, there is limited information on the formation and clearance dynamics of tau inclusions. Using rAAV vectors to mediate expression of Dendra2-tagged human wild-type, P301L and pro-aggregant P301L/S320F tau proteins, with and without the addition of exogenous tau fibrillar seeds, we evaluated tau inclusion dynamics in organotypic brain slice culture (BSC) models using long-term optical pulse labeling methodology. Our studies reveal that tau inclusions typically form in 12-96 h in tauopathy BSC models. Unexpectedly, we demonstrate appreciable turnover of tau within inclusions with an average half-life of ~ 1 week when inclusions are newly formed. When BSCs with inclusions are aged in culture for extended periods, tau inclusions continue to turnover, but their half-lives increase to ~ 2 weeks and ~ 3 weeks after 1 and 2 months in culture, respectively. Individual tau inclusions can be long-lived structures that can persist for months in these BSC models and for even longer in the human brain. However, our data indicate that tau inclusions, are not 'tombstones', but dynamic structures with appreciable turnover. Understanding the cellular processes mediating this inclusion turnover may lead to new therapeutic strategies that could reverse pathological tau inclusion formation.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Croft CL,Goodwin MS,Ryu DH,Lessard CB,Tejeda G,Marrero M,Vause AR,Paterno G,Cruz PE,Lewis J,Giasson BI,Golde TEdoi
10.1007/s00401-021-02264-9subject
Has Abstractpub_date
2021-01-26 00:00:00eissn
0001-6322issn
1432-0533pii
10.1007/s00401-021-02264-9pub_type
杂志文章abstract：:To investigate the pathogenetic role of human T lymphocyte virus type I (HTLV-I) in central nervous system disease, a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis, designated as HAM rat disease, has been established. Wistar-King-Aptekman-Hokudai strain rats with induced HTLV-I infection deve...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050962
更新日期：1999-02-01 00:00:00
abstract：:Flurothyl-induced status epilepticus was studied by light and electron microscopy (LM, EM) to determine the time course and structural features of neuronal necrosis in the vulnerable brain regions in epilepsy. The cerebral cortex, hippocampus and thalamus were examined after closely spaced recovery periods of up to 1 ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687789
更新日期：1988-01-01 00:00:00
abstract：:Synucleinopathies, such as Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), are defined by the presence of α-synuclein (αSYN) aggregates throughout the nervous system but diverge from one another with regard to their clinical and pathological phenotype. The recent generatio...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-020-02157-3
更新日期：2020-06-01 00:00:00
abstract：:Motor neuron disease (MND) may be complicated by frontotemporal dementia and/or an extrapyramidal movement disorder. Several studies have identified the pathological substrate for dementia in MND as being ubiquitin-immunoreactive inclusions and dystrophic neurites in the extramotor neocortex and hippocampus. Although ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-003-0814-y
更新日期：2004-04-01 00:00:00
abstract：:The dynamics of cerebrospinal fluid (CSF) tau and Aβ biomarkers over time in Alzheimer's disease (AD) patients from prodromal pre-symptomatic to severe stages of dementia have not been clearly defined and recent studies, most of which are cross-sectional, present conflicting findings. To clarify this issue, we analyze...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-013-1151-4
更新日期：2013-11-01 00:00:00
abstract：:Foetal rat brain reaggregate cultures have been employed to investigate the morphological changes associated with the neurotoxic action of ethylcholine mustard aziridinium (ECMA). In a companion study we provided evidence for apparent selective cholinergic neurotoxicity. Exposure of 9-day-old cultures to 12.5 microM E...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00334882
更新日期：1993-01-01 00:00:00
abstract：:The extent of DNA fragmentation analysed using the TUNEL technique was evaluated in post-mortem human brain tissue. Twenty-four patients with clinical and histopathological diagnosis of Alzheimer's disease (AD) and a short post-mortem delay were analysed. We report an increase in the count of TUNEL-labelled cells as t...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010000228
更新日期：2000-12-01 00:00:00
abstract：:A desmoplastic primary cerebral neuroblastoma originating in the frontal lobe of a boy who died at the age of 6 years contained dense core vesicles within the cytoplasm of neoplastic cells as evidence of neuronal differentiation. Sarcomatous transformation had occurred at the time of recurrence. At autopsy, he also ha...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688540
更新日期：1980-01-01 00:00:00
abstract：:The essential role of the cellular prion protein (PrPC) in prion disorders such as Creutzfeldt-Jakob disease is well documented. Moreover, evidence is accumulating that PrPC may act as a receptor for protein aggregates and transduce neurotoxic signals in more common neurodegenerative disorders, such as Alzheimer's dis...
journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s00401-017-1790-y
更新日期：2018-02-01 00:00:00
abstract：:Intermitochondrial septate structures were found in the dystrophic axons of two cases of infantile neuroaxonal dystrophy. Septate structures were previously seen in some tumors (glioblastomas and Schwannomas) and several organs of vertebrates and invertebrates, but never in human central nervous system (CNS). The stru...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688007
更新日期：1980-01-01 00:00:00
abstract：:Little information is available regarding the morphological changes in the mitochondria in amyotrophic lateral sclerosis (ALS). In particular, mitochondrial changes in dorsal root ganglion cells have not yet been examined. We therefore conducted an electron microscopic examination of the mitochondria in dorsal root ga...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-007-0299-1
更新日期：2007-12-01 00:00:00
abstract：:Cerebral cortical lesions of tuberous sclerosis (TSC) and focal cortical dysplasia (FCD) show disturbances in laminar architecture and cellular differentiation. We immunohistochemically studied the expression of doublecortin, a fetal neuronal protein that regulates neuronal migration, in the surgical specimens of five...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-002-0575-z
更新日期：2002-10-01 00:00:00
abstract：:Hyper- and hypothyroidism repercussions on soma, nucleus and cytoplasm increases were studied by electron microscopy on 7-, 14-, 21-, and 35-day-old rats. Adult normal animals were compared with adult ones made hypothyroid until they were 35 days old. Also heat value restriction of food intake effects were compared wi...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：
更新日期：1978-09-15 00:00:00
abstract：:Most cases of frontotemporal lobar degeneration (FTLD) are characterized by abnormal intracellular accumulation of either tau or TDP-43 protein. However, in ~10% of cases, composed of a heterogenous collection of uncommon disorders, the molecular basis remains to be uncertain. We recently discovered that the pathologi...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-010-0764-0
更新日期：2011-02-01 00:00:00
abstract：:Neuroaxonal spheroids became evident microscopically after the autopsy of a 45-year-old woman with pigmentation of the globus pallidus suggesting Hallervorden-Spatz disease. In our opinion the fine floccular pigment seen electron-microscopically in many of the axonal spheroids is melanin, an end product of catecholami...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691981
更新日期：1983-01-01 00:00:00
abstract：:Olfactory dysfunction is a frequent and early feature of patients with neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) and is very uncommon in patients with frontotemporal dementia (FTD). Mechanisms underlying this clinical manifestation are poorly understood but the premature...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-011-0830-2
更新日期：2011-07-01 00:00:00
abstract：:Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687372
更新日期：1989-01-01 00:00:00
abstract：:We examined whether the Golgi apparatus (GA) is fragmented in nigral neurons in 18 cases with Parkinson's disease (PD) and in 8 control cases. The nigral neurons in cases with PD showed various degrees of Lewy pathology with alpha-synuclein immunohistochemistry, and we divided the neurons into three subtypes according...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-006-0114-4
更新日期：2006-09-01 00:00:00
abstract：:Peroxidase-labeled lectins were used for detection of specific monosaccharide residues in amyloid plaques in brains of scrapie-infected mice. The lectins tested recognize the following residues: beta-D-galactosyl (Ricinus communis agglutinin 120, RCA-1), alpha-D-galactosyl and alpha-D-galactopyranoside (Bandeirea simp...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688295
更新日期：1986-01-01 00:00:00
abstract：:To determine the origin of the large myelinated fibers in the anterolateral funiculus (ALF) in the spinal cord of humans, myelinated fibers in the ALF of the mid-cervical spinal cord were examined quantitatively. Five groups of subjects were examined, consisting of control subjects, patients with cerebral lesions and ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010051129
更新日期：1999-12-01 00:00:00
abstract：:A unique pathological finding of astrocytes was observed in the brain of a 20-year-old man who had severe physical and mental retardation. The brain was malformed showing micropolygyria in several cortical areas. A large number of hypertrophic astrocytes with eosinophilic granular substances in their cytoplasm were fo...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00427225
更新日期：1992-01-01 00:00:00
abstract：:Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010000332
更新日期：2001-06-01 00:00:00
abstract：:This report deals with the expression of stress-response (heat-shock) protein 72 (srp 72) in a series of 95 primary human brain tumors and 21 carcinoma metastases to the central nervous system (CNS). Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 were used as positive con...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00227818
更新日期：1992-01-01 00:00:00
abstract：:This study was undertaken to elucidate, using the Golgi method, the neuropathological change in the brain of the macular mutant mouse, whose hemizygote (Ml/y) is considered to be a model of Menkes kinky hair disease (MKHD). The hemizygote mice gradually lost weight after 10 days of age and died with emaciation and sei...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687266
更新日期：1987-01-01 00:00:00
abstract：:The presence of many neurofibrillary tangles (NFTs) in the central nervous system is a hallmark of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) in people living in the Kii peninsula of Japan and in the island of Guam. To determine whether or not ALS and PDC are on a spectrum of a single ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-007-0197-6
更新日期：2007-06-01 00:00:00
abstract：:The close correlation between abnormally low pre-mortem cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ(1-42)) and plaque burden measured by amyloid imaging as well as between pathologically increased levels of CSF tau and the extent of neurodegeneration measured by MRI has led to growing interest in usi...
journal_title：Acta neuropathologica
pub_type： 杂志文章,多中心研究
doi：10.1007/s00401-011-0808-0
更新日期：2011-05-01 00:00:00
abstract：:The thoracic sympathetic preganglionic outflow is important in the maintenance of postural normotension in man. Normative data on the intermediolateral column (ILC) neuron cell bodies is lacking. Counts and measurements on the right ILC cytons have been performed on the T6, T7 and T8 segments of 12 spinal cords of man...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688573
更新日期：1977-09-26 00:00:00
abstract：:The isolated paired helical filaments (PHF) that occur in the neurofibrillary tangles of Alzheimer's disease were assayed to determine if they contained N-acetyl-glucosamine and N-acetyl-galactosamine residues. The enzyme-linked lectin assay was used to detect their total content in the PHF preparation. The assay empl...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00294242
更新日期：1990-01-01 00:00:00
abstract：:Using a 3H-labelled virion DNA probe applied to tissue sections, we have previously identified the precise microscopic anatomical location of herpes simplex virus (HSV) during the acute and latent stages of infection of the mouse trigeminal ganglia and central nervous system (CNS). In the present investigation, we com...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00692842
更新日期：1987-01-01 00:00:00
abstract：:A case history illustrating the potential clinical significance of subependymoma is presented. Fine structural studies indicate that the tumor is composed of cells having the cytoplasmic features of ependyma, astrocytes, and transitional cells. Its composition and structure are alike those in the adult mammalian subep...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691968
更新日期：1977-11-28 00:00:00
