Tau‐like immunoreactivity in Alzheimer and control skin fibroblasts

Matsuyama, Steven S.; Bondareff, William

doi:10.1002/jnr.490390503

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…The microtubule-associated protein (MAP) tau is mainly found in the brain and spinal cord, but is also found at relatively high levels in heart, skeletal muscle, lung, kidney and testis and at much lower levels in adrenal gland, stomach, liver, spleen and fibroblasts (Montejo et al 1986;Tucker 1990;Ashman et al 1992;Lee and Rook 1992;Lubke et al 1994;Matsuyama and Bondareff 1994;Gu et al 1996). Tau is highly enriched in axonal compartments (especially in mature neurons; Fig.…”

Section: Discussionmentioning

confidence: 99%

Amyloid‐β‐induced toxicity of primary neurons is dependent upon differentiation‐associated increases in tau and cyclin‐dependent kinase 5 expression

Liu

Perry

Chan

et al. 2003

Journal of Neurochemistry

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It has previously been reported that amyloid-b (Ab) peptide is neurotrophic to undifferentiated but neurotoxic to differentiated primary neurons. The underlying reasons for this differential effect is not understood. Recently, the toxicity of Ab to neurons was shown to be dependent upon the activation of cyclindependent kinase 5 (Cdk5), thought to promote tau phosphorylation that leads to cytoskeletal disruption, morphological degeneration and apoptosis. Here we report that Cdk5, tau, and phosphorylated-tau (P-tau) are expressed at very low levels in undifferentiated primary neurons, but that the expression of Cdk5 and tau and the phosphorylation of tau increase markedly between 4 and 8 days of differentiation in vitro. Tau expression decreased after this time, as did the level of P-tau, to low levels by 17 days. Ab induced tau phosphorylation of neurons only after ‡ 4 days of differentiation, a time that coincides with the onset of Ab toxicity. Blocking tau expression (and therefore tau phosphorylation) with an antisense oligonucleotide completely blocked Ab toxicity of differentiated primary neurons, thereby confirming that tau was essential for mediating Ab toxicity. Our results demonstrate that differentiation-associated changes in tau and Cdk-5 modulate the toxicity of Ab and explain the opposite responses of differentiated and undifferentiated neurons to Ab. Our results predict that only cells containing appreciable levels of tau are susceptible to Ab-induced toxicity and may explain why Ab is more toxic to neurons compared with other cell types.

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Section: Discussionmentioning

confidence: 99%

Amyloid‐β‐induced toxicity of primary neurons is dependent upon differentiation‐associated increases in tau and cyclin‐dependent kinase 5 expression

Liu

Perry

Chan

et al. 2003

Journal of Neurochemistry

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“…Although process extension was not directly examined in this previous study, it is therefore likely that the formation of cellular processes by ras-transformed cells does not require increased expression levels of tubulin or microtubule-associated proteins. Similarly, although recent studies have shown that proteins with antigenic similarity to neuronal tau are expressed by fibroblasts [Ingelson et al, 1996;Matsuyama and Bondareff, 1994], these proteins are expressed in fibroblasts only at low levels and their function in this cell type has not been determined. Higher expression levels of the microtubule-associated protein MAP4 are expressed in fibroblast [Bulinksi and Borisy, 1980], and MAP4 could therefore play a role in stabilizing microtubules within processes observed in the present study.…”

Section: Process Extension Mechanisms Are Similar In Different Cell Typesmentioning

confidence: 99%

Major role for active extension in the formation of processes byras-transformed fibroblasts

Shelden

1999

Cell Motil. Cytoskeleton

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Expression of constitutively active Ras protein in fibroblasts results in enhanced cell motility, invasion competence and morphological changes including the formation of elongate cellular processes. These processes have been shown to resemble retraction tails formed passively behind nontransformed cells by movement relative to sites of cell-substrate attachment. However, analysis presented here reveals that active extension mechanisms also play a role in the formation of these processes. Extension of distal process ends occurs at 0.42 Ϯ 0.44 µm/min in ras-transformed fibroblasts and accounts for 63.6 Ϯ 27.5% of observed process lengths. Active process extension by ras-transformed fibroblasts also persists in the presence of cell-cell contacts. Studies conducted using actin or microtubule antagonists, and correlation of process behavior followed by fixation and immunostaining reveal that process extension requires intact actin and microtubule networks. Other analyses reveal that active extension plays a significantly smaller role in the formation of processes by non-transformed control fibroblasts. These observations demonstrate that constitutively active Ras enhances process extension in fibroblasts and is a causal factor in process extension by fibroblasts in the presence of cell-cell contacts. Moreover, these studies demonstrate that process extension by ras-transformed fibroblasts is accomplished through mechanisms similar to those thought to drive active extension of processes by other cell types including neurons. These findings suggest that extension of cellular processes could play an important role in the metastatic behavior of ras-transformed fibroblasts as well as the response of untransformed fibroblasts to receptor mediated signal transduction events.

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“…Proposed functions for peripheral tau include transcriptional involvement in leukocytes and regulation of signal transduction in a neuroblastoma cell line [10,11]. Presence of tau has also been demonstrated in human fibroblasts [9,12,13] but tau levels in fibroblast lysates from individuals with AD were not elevated compared to controls [9], indicating that disturbed metabolism of tau in AD probably is CNS specific.…”

Section: Introductionmentioning

confidence: 99%

<i>Tau</i> Immunoreactivity Detected in Human Plasma, But No Obvious Increase in Dementia

Ingelson

Blomberg

Benedikz

et al. 1999

Dement Geriatr Cogn Disord

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Tau proteins are central to the neuropathology of Alzheimer’s disease and tau levels in cerebrospinal fluid are elevated in affected individuals. In this study, we investigated the presence of tau in plasma from subjects with Alzheimer’s disease (n = 16), frontotemporal dementia (n = 10), vascular dementia (n = 16) and from healthy controls (n = 15). By using an ELISA with monoclonal tau antibodies, tau immunoreactivity was detected in approximately 20% of the subjects. However, no difference between the disease and control groups was seen. After gel filtration of tau immunopositive plasma, the peak reactivity was found in the 160-kD fraction, indicating the source to be tau-like molecules of high-molecular-weight or polymers of low-molecular-weight tau isoforms. We conclude that measurements of tau in plasma cannot be utilized diagnostically for Alzheimer’s disease or for the other dementias investigated.

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Tau‐like immunoreactivity in Alzheimer and control skin fibroblasts

Cited by 10 publications

References 30 publications

Amyloid‐β‐induced toxicity of primary neurons is dependent upon differentiation‐associated increases in tau and cyclin‐dependent kinase 5 expression

Amyloid‐β‐induced toxicity of primary neurons is dependent upon differentiation‐associated increases in tau and cyclin‐dependent kinase 5 expression

Major role for active extension in the formation of processes byras-transformed fibroblasts

<i>Tau</i> Immunoreactivity Detected in Human Plasma, But No Obvious Increase in Dementia

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