SEARCH · PubMed Health

Results for “Phosphorylated tau”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2006

CSF biomarkers for Alzheimer's Disease: levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival.

UNLABELLED: Cerebrospinal fluid (CSF) samples from 21 patients with a clinical diagnosis of Alzheimer's disease (AD) participating in a 5-year treatment study with the choline esterase inhibitor tacrin were retrospectively analyzed for the contents of beta-amyloid (Abeta42), total tau (T-tau) and phosphorylated tau (P-tau). A significant positive correlation between the level of P-tau and the number of symptoms according to the DSM-IV criteria (p = 0.041) and the NINCDS-ADRDA (p = 0.029) was observed (i.e. higher levels were found in cases with more symptoms). A significant positive correlation between T-tau, P-tau and ADAS-cog score was identified (i.e. higher levels were found with more severe cognitive dysfunction). Patients who died during the 5-year follow-up had significantly lower levels of Abeta42 (p = 0.011) than those who were still alive. Patients who had died in a 6-year follow-up had significantly lower levels of Abeta42 (p = 0.034) and higher levels of T-tau (p = 0.041) than patients still alive. CONCLUSION: CSF biomarkers do aid the clinical diagnosis of AD. Increased levels of P-tau and T-tau are possible markers for severity and abundance of symptoms in AD. Low levels of Abeta42 may indicate a higher risk of early death in AD.

Aged↗

PubMed2000

Cyclin-dependent kinase 5 colocalizes with phosphorylated tau in human inclusion-body myositis paired-helical filaments and may play a role in tau phosphorylation.

To investigate the possible role of cyclin-dependent kinase 5 (cdk5) in the formation of paired helical filaments (PHFs) in muscle of patients with inclusion-body myositis (IBM), we immunolocalized cdk5, by light- and electron- microscopy, in muscle biopsies of six IBM patients. Approximately 80-90% of IBM vacuolated muscle fibers, and 10-15% of nonvacuolated fibers, contained well defined cdk5-immunoreactive inclusions that colocalized with phosphorylated tau in 70-80% of those fibers. Immunoelectronmicroscopy revealed the association of cdk5 with tau-immunoreactive PHFs. In all biopsies that contained them, regenerating muscle fibers had diffuse, moderate to strong cdk5 immunoreactivity. At all neuromuscular junctions, there was strong cdk5 immunoreactivity postsynaptically. Our study suggests that cdk5: (1) plays a role in IBM pathogenesis, possibly mediating phosphorylation of PHF-related tau; (2) is involved in muscle regeneration; and (3) has a novel function at normal neuromuscular junctions.

Cyclin-Dependent Kinase 5↗

PubMed2003

Total tau and phosphorylated tau 181 levels in the cerebrospinal fluid of patients with frontotemporal dementia due to P301L and G272V tau mutations.

BACKGROUND: Frontotemporal dementia (FTD) is a pathologically heterogeneous group of presenile neurodegenerative disorders, with or without the deposition of hyperphosphorylated tau protein in affected brain regions. Mutations in the tau gene have been found in the familial form of FTD, linked to chromosome 17q21-22, showing a spectrum of tauopathy. OBJECTIVE: To evaluate levels of total tau, phosphorylated tau 181 (Ptau-181), and amyloid-beta1-42 in the cerebrospinal fluid (CSF) of patients with FTD, with special emphasis on FTD due to tau mutations. DESIGN: Case-control study. SETTING: Outpatient neurology clinics at 2 university medical centers, in Rotterdam and Amsterdam (the Netherlands). PATIENTS: Twenty-six patients with FTD (9 with tau mutations 7 P301L and 2 G272V), 18 patients with Alzheimer disease (AD), and 13 nondemented controls. METHODS: Total tau, Ptau-181, and amyloid-beta1-42 levels in CSF, obtained by lumbar puncture, were determined by sandwich enzyme-linked immunosorbent assay. Patients were diagnosed after clinical examination, neuropsychologic evaluation, and neuroimaging. Differences between patient groups were statistically evaluated using nonparametric tests. RESULTS: Although CSF levels of total tau were mildly increased in FTD patients compared with nondemented controls (P =.05), median CSF total tau levels were low in the subgroup with tau mutations compared with AD patients. Furthermore, CSF levels of Ptau-181 and amyloid-beta1-42 were not different in FTD patients, including the patients with tau mutations, compared with nondemented controls. CONCLUSIONS: The tauopathy in P301L and G272V does not appear to be associated with an evident increase in CSF levels of Ptau-181 in FTD patients with these tau mutations, in contrast with findings in patients with AD.

Aged↗

PubMed2005

CSF Abeta42 and tau or phosphorylated tau and prediction of progressive mild cognitive impairment.

Baseline CSF amyloid beta-peptide-42 (Abeta42), tau, and phosphorylated tau (P-tau) levels from 46 control subjects and 78 patients with mild cognitive impairment (MCI) were measured. Twenty-three patients with MCI developed dementia during the study. Abnormal biomarkers were found early in the course of Alzheimer disease (AD). The most predictive assay for AD among the patients with MCI was the combination of Abeta42 and P-tau.

Aged↗

PubMed2006

CSF Abeta42, Tau and phosphorylated Tau, APOE epsilon4 allele and MCI type in progressive MCI.

BACKGROUND: The patients with mild cognitive impairment (MCI) have an elevated risk for Alzheimer's disease (AD). Especially the amnestic MCI is seen as prodrome of AD. Apolipoprotein E (APOE) epsilon4 allele, abnormal CSF Abeta42, Tau and phosphorylated Tau (phospho-Tau) levels are associated with elevated risk for AD. METHODS: APOE genotyping was done by PCR based method and baseline CSF Abeta42, Tau and phospho-Tau were measured by ELISA from 60 controls and 79 MCI patients. RESULTS: Thirty-three MCI patients developed dementia during an average of 3.5 years follow-up. CSF Abeta42 was decreased and Tau and phospho-Tau were increased in the progressive MCI patients. The APOE epsilon4 allele was more frequent in the progressive MCI patients. The APOE epsilon4 allele showed a dose dependent association o the Abeta42 levels in the progressive MCI patients and to all of the markers in controls. CONCLUSIONS: Decreased CSF Abeta42 and elevated Tau or phospho-Tau together with APOE epsilon4 allele are highly predictive for the dementia in MCI patients with amnestic or executive symptoms.

Aged↗

PubMed1993

Developmental changes in tau phosphorylation: fetal tau is transiently phosphorylated in a manner similar to paired helical filament-tau characteristic of Alzheimer's disease.

Rat and human fetal brain tau were probed with a panel of monoclonal antibodies (tau-1, AT8, 8D8, RT97, SMI31, SMI34) that distinguish between paired helical filament (PHF)-tau of Alzheimer's disease and normal adult brain tau. These antibodies discriminate between normal and PHF-tau because their epitopes are phosphorylated in PHF-tau. Although only one molecular isoform of tau was shown to be expressed in fetal brain, two fetal tau species could be distinguished on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the slower migrating species was recognized by all of the PHF-tau-specific antibodies. Moreover, this immunoreactivity was shown to be phosphorylation dependent. Our observations suggest that the abnormal phosphorylation of tau in Alzheimer's disease may be the result of reactivation of pathways governing the phosphorylation of tau in the developing brain.

Adult↗

PubMed2006

14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan.

1. Sporadic Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal disease. Patients with CJD usually become akinetic mutism within approximately 6 months. In addition, clinical signs and symptoms at early stage of sporadic CJD may not be easy to distinguish from other neurodegenerative diseases by neurological findings. However, diagnostic biochemical parameters including 14-3-3 protein, S100, neuron-specific enorase in cerebrospinal fluid (CSF) have been used as diagnostic markers, elevated titers of these markers can also be observed in CSF in other neurodegenerative diseases. Therefore, we examined other biochemical markers to discriminate CJD from other neurodegenerative diseases in CSF. 2. We analyzed CSF samples derived from 100 patients with various neurodegenerative disorders by Western blot of 14-3-3 protein, quantification of total tau (t-tau) protein, and phosphorylated tau (p-tau) protein. All patients with CJD in this study showed positive 14-3-3 protein and elevated t-tau protein (>1000 pg/mL) in CSF. We also detected positive 14-3-3 protein bands in two patients in non-CJD group (patients with dementia of Alzheimer's type; DAT) and also detected elevated t-tau protein in three patients in non-CJD group. Elevated t-tau protein levels were observed in two patients with DAT and in one patient with cerevrovascular disease in acute phase. 3. To distinguish patients with CJD from non-CJD patients with elevated t-tau protein in CSF, we compared the ratio of p-tau and t-tau proteins. The p-/t-tau ratio was dramatically and significantly higher in DAT patients rather than in CJD patients. 4.Therefore, we concluded that the assay of t-tau protein may be useful as 1st screening and the ratio of p-tau protein/t-tau protein would be useful as 2nd screening to discriminate CJD from other neurodegenerative diseases.

14-3-3 Proteins↗

PubMed2005

Dynamic changes of phosphorylated tau in mouse hippocampus after cold water stress.

The abnormal hyperphosphorylation of tau protein in brain is attributed to a number of neurodegenerative diseases such as Alzheimer disease. It has been reported that cold water stress (CWS) could cause rapid reversible tau phosphorylation in brain. To explore the possible long-tem effects of CWS on tau phosphorylation, we employed the immunoblot and immunohistochemical methods to analyze the phosphorylation of tau in the hippocampus of mice subjected to CWS. Results showed that CWS stimulation caused not only an early phase reversible tau phosphorylation, but also a later phase tau phosphorylation after 6h. The distribution pattern of phosphorylated tau (P-tau) in the later phase was different to that of early phase. At 1h after CWS, defined as early phase, P-tau was strikingly located in the mossy fibers and nerve terminals at the molecular layer of dentate gray (DG), whereas at 12h, defined as later phase, P-tau was dominantly located in the somatodendritic compartments of neurons in DG and CA3/CA1 regions, but obviously decreased in the mossy fibers and nerve terminals of molecular layer. These findings demonstrate that CWS leads to prominent changes of tau phosphorylation and P-tau localization in the hippocampus in a time dependent manner.

Alzheimer Disease↗

PubMed2004

Linking alterations in tau phosphorylation and cleavage during neuronal apoptosis.

Neurofibrillary tangles (NFTs) are classic lesions of Alzheimer's disease. NFTs are bundles of abnormally phosphorylated tau, the paired helical filaments. The initiating mechanisms of NFTs and their role in neuronal loss are still unknown. Accumulating evidence supports a role for the activation of proteolytic enzymes, caspases, in neuronal death observed in brains of patients with Alzheimer's disease. Alterations in tau phosphorylation and tau cleavage by caspases have been previously reported in neuronal apoptosis. However, the links between the alterations in tau phosphorylation and its proteolytic cleavage have not yet been documented. Here, we show that, during staurosporine-induced neuronal apoptosis, tau first undergoes transient hyperphosphorylation, which is followed by dephosphorylation and cleavage. This cleavage generated a 10-kDa fragment in addition to the 17- and 50-kDa tau fragments previously reported. Prior tau dephosphorylation by a glycogen synthase kinase-3beta inhibitor, lithium, enhanced tau cleavage and sensitized neurons to staurosporine-induced apoptosis. Caspase inhibition prevented tau cleavage without reversing changes in tau phosphorylation linked to apoptosis. Furthermore, the microtubule depolymerizing agent, colchicine, induced tau dephosphorylation and caspase-independent tau cleavage and degradation. Both phenomena were blocked by inhibiting protein phosphatase 2A (PP2A) by okadaic acid. These experiments indicate that tau dephosphorylation precedes and is required for its cleavage and degradation. We propose that the absence of cleavage and degradation of hyperphosphorylated tau (due to PP2A inhibition) may lead to its accumulation in degenerating neurons. This mechanism may contribute to the aggregation of hyperphosphorylated tau into paired helical filaments in Alzheimer's disease where reduced PP2A activity has been reported.

Alzheimer Disease↗

PubMed2006

Total tau protein, phosphorylated tau (181p) protein, beta-amyloid(1-42), and beta-amyloid(1-40) in cerebrospinal fluid of patients with dementia with Lewy bodies.

The intra vitam diagnosis of different dementias is still based on clinical grounds. So far, no technical investigations have been available to support these diagnoses. For tau protein and beta-amyloid(1-42) in cerebrospinal fluid (CSF), promising results for the diagnosis of Alzheimer's disease (AD) have been reported; however, their differential diagnostic spectrum is limited, as was recently shown for dementia with Lewy bodies (DLB) and for AD. Therefore, further marker proteins have to be established to ameliorate, support, and differentiate these clinical diagnoses. We evaluated beta-amyloid(1-40) and phosphorylated tau protein (181p), in addition to total tau protein and beta-amyloid(1-42), in 20 patients with DLB, 34 AD patients, and 20 non-demented neurological controls (NDCs). All markers could differentiate between the dementia groups (AD, DLB) and the controls. AD and DLB could be differentiated only by levels of total tau protein and by the ratio total tau protein/phosphorylated tau protein. However, values still overlapped markedly. In some cases, tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited, especially because of mixed pathology. We conclude that more specific markers have to be established to differentiate between these diseases.

Aged↗

PubMed2002

Apolipoprotein E and Reelin ligands modulate tau phosphorylation through an apolipoprotein E receptor/disabled-1/glycogen synthase kinase-3beta cascade.

Neurofibrillary tangles comprised of highly phosphorylated tau proteins are a key component of Alzheimer's disease pathology. Mice lacking Reelin (Reln), double-knockouts lacking the VLDL receptor (VLDLR) and ApoE receptor2 (ApoER2), and mice lacking disabled-1 (Dab1) display increased levels of phosphorylated tau. Because Reln binds to recombinant ApoE receptors, assembly of a Reln/ApoE-receptor/Dab1 (RAD) complex may initiate a signal transduction cascade that controls tau phosphorylation. Conversely, disruption of this RAD complex may increase tau phosphorylation and lead to neurodegeneration. To substantiate this concept, we mated Reln-deficient mice to ApoE-deficient mice and found that in the absence of Reln, tau phosphorylation increased as the amount of ApoE decreased. Paralleling the change in tau phosphorylation levels, we found that GSK-3beta activity increased in Reln-deficient mice and further increased in mice lacking both Reln and ApoE. CDK-5 activity was similar in mice lacking Reln, ApoE, or both. GSK-3beta and CDK-5 activity increased in Dab1-deficient mice, independent of ApoE levels. Further supporting the idea that increased tau phosphorylation results primarily from increased kinase activity, the activity of two phosphatases was similar in all conditions tested. These data support a novel, ligand-mediated signal transduction cascade--initiated by the assembly of a RAD complex that suppresses kinase activity and controls tau phosphorylation.

Animals↗

PubMed2000

Muscarinic agonists reduce tau phosphorylation in non-neuronal cells via GSK-3beta inhibition and in neurons.

Muscarinic agonists alter the metabolism of amyloid precursor protein, leading to an increase in alpha-secretase cleavage and a decreased production of amyloidogenic peptides; suggesting that these compounds might modify the Alzheimer's disease process. A second therapeutic target in AD is the accumulation of stably phosphorylated tau into neurofibrillary tangles; an early event correlating with cognitive impairment. Glycogen synthase kinase-3 (GSK-3beta) phosphorylates tau and is inhibited via protein kinase C (PKC). As certain muscarinic receptors are linked to PKC, we examined the effect of a range of agonists on GSK-3beta phosphorylation of tau. In neurons a nonspecific muscarinic agonist, carbachol, reduced tau phosphorylation. In nonneuronal cells expressing the ml receptor a range of ml agonists reduced transiently-expressed tau phosphorylation and altered its microtubulebinding properties. These findings link the two pathological process of AD-APP metabolism and tau phosphorylation - and suggest that muscarinic and other cholinergic compounds might have disease-modifying properties.

Acetylcholine↗

PubMed1995

Sodium butyrate induces aberrant tau phosphorylation and programmed cell death in human neuroblastoma cells.

Paired helical filaments, one of the major hallmarks of Alzheimer's disease brains at autopsy, consist mainly of aberrantly phosphorylated tau. This aberrant tau phosphorylation can be induced in the human neuroblastoma cell line TR14 by a hyperstimulating mixture, consisting of nerve growth factor (NGF), db-cAMP, gangliosides and sodium butyrate (NaBut) [20,23]. Evidence is presented that exposing these cells to increasing concentrations of NaBut alone in the 0.5-2 mM dose-range is sufficient to induce aberrant tau phosphorylation within 24 h, measured by AT-8 immunocytochemistry and Western blotting. This process is associated with increased morphological differentiation. Furthermore, the aberrant tau phosphorylation is followed by neurotoxicity. This neurotoxicity has features of programmed cell death, such as fragmentation on a DNA agarose gel, fragmented nuclei and chromatin condensation and inhibition by the protein synthesis inhibitor cycloheximide. The mechanism by which NaBut induces these modified tau proteins and neurotoxicity are largely unknown but the data suggest an involvement of cytoskeletal proteins.

Antibodies, Monoclonal↗

PubMed2006

Increased tau phosphorylation at the Ser396 epitope after amyloid beta-exposure in organotypic cultures.

The hallmarks of Alzheimer's disease include extracellular plaques primarily consisting of amyloid-beta peptide and intracellular neurofibrillary tangles composed of highly phosphorylated tau protein. We report that exposure of organotypic hippocampal cultures to synthetic amyloid-beta peptide(25-35) (50 microM, 96 h) causes neurodegeneration concomitant with a significant increase in tau phosphorylation at the Ser epitope (+60%). Furthermore, the level of active glycogen synthase kinase-3beta (GSK-3beta [pTyr]) was increased (+55%) after amyloid-beta peptide(25-35) exposure. These findings support the role of amyloid-beta peptide as a mediator of tau phosphorylation and demonstrate the usefulness of organotypic cultures for investigating the link between amyloid-beta peptide-induced neurotoxicity and tau phosphorylation. Our results also confirm that amyloid-beta peptide induces activation of glycogen synthase kinase-3beta.

Amyloid beta-Peptides↗

PubMed2003

Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway.

The presence of tangles of abnormally phosphorylated tau is a characteristic of Alzheimer's disease (AD), and the loss of synapses correlates with the degree of dementia. In addition, the overexpression of interleukin-1 (IL-1) has been implicated in tangle formation in AD. As a direct test of the requirement for IL-1 in tau phosphorylation and synaptophysin expression, IL-1 actions in neuron-microglia cocultures were manipulated. Activation of microglia with secreted beta-amyloid precursor protein or lipopolysaccharide elevated their expression of IL-1alpha, IL-1beta, and tumor necrosis factor alpha (TNFalpha) mRNA. When such activated microglia were placed in coculture with primary neocortical neurons, a significant increase in the phosphorylation of neuronal tau was accompanied by a decline in synaptophysin levels. Similar effects were evoked by treatment of neurons with recombinant IL-1beta. IL-1 receptor antagonist (IL-1ra) as well as anti-IL-1beta antibody attenuated the influence of activated microglia on neuronal tau and synaptophysin, but anti-TNFalpha antibody was ineffective. Some effects of microglial activation on neurons appear to be mediated by activation of p38 mitogen-activated protein kinase (p38-MAPK), because activated microglia stimulated p38-MAPK phosphorylation in neurons, and an inhibitor of p38-MAPK reversed the influence of IL-1beta on tau phosphorylation and synaptophysin levels. Our results, together with previous observations, suggest that activated microglia may contribute to neurofibrillary pathology in AD through their production of IL-1, activation of neuronal p38-MAPK, and resultant changes in neuronal cytoskeletal and synaptic elements.

Amyloid beta-Protein Precursor↗

PubMedDate not supplied

Neuronal kinase stimulation leads to aberrant tau phosphorylation and neurotoxicity.

Neurofibrillary tangles in Alzheimer's disease brain consist mainly of abnormally phosphorylated tau proteins organised in paired helical filaments. Induction of tau phosphorylation in living neurons by hyperstimulation is monitored by specific monoclonal antibodies, such as AT-8 and PHF-1. By quantitative immunocytochemistry, we show that aberrant phosphorylation at the Ser199/Ser202 epitope (AT-8) and at the Ser 396 epitope (PHF-1) are moderately induced, proportionally to the degree of kinase stimulation. Whereas AT8 expression is prominent after 48 h, cell death becomes significant at 72 h and is related to the degree of stimulation and the expression level of aberrant tau phosphorylation. Time-lapse videomicroscopy of individual neuroblastoma cells suggest that hyperstimulation leads to a form of morphological over-differentiation. Immediately before cell death, some cells tend to display some features of mitosis. The data suggest a strong correlation between the expression of specific PHF-epitopes and subsequent cell death. The extended time scale of toxicity in this model may be appropriate to study in more detail the steps leading to aberrant phosphorylation associated neurotoxicity.

Animals↗

PubMed2002

Abnormal Tau phosphorylation of the Alzheimer-type also occurs during mitosis.

In Alzheimer's disease, neurofibrillary degeneration results from the aggregation of abnormally phosphorylated Tau proteins into filaments and it may be related to the reactivation of mitotic mechanisms. In order to investigate the link between Tau phosphorylation and mitosis, Xenopus laevis oocytes in which most of the M-phase regulators have been discovered were used as a cell model. The human Tau isoform htau412 (2+3-10+) was microinjected into prophase I oocytes that were then stimulated by progesterone that activate cyclin-dependent kinase pathways. Hyperphosphorylation of the Tau isoform, which is characterized by a decrease of its electrophoretic mobility and its labelling by a number of phosphorylation-dependent antibodies, was observed at the time of germinal vesicle breakdown. Surprisingly, Tau immunoreactivity, considered as typical of Alzheimer's pathology (AT100 and phospho-Ser422), was observed in meiosis II. Because meiosis II is considered as a mitosis-like phase, we investigated if our observation was also relevant to a neurone-like model. Abnormal Tau phosphorylation was detected in mitotic human neuroblastoma SY5Y cells overexpressing Tau. Regarding AT100-immunoreactivity and phospho-Ser422, we suggest that phosphatase 2A inhibition and a phosphorylation combination of mitotic kinases may lead to this Alzheimer-type phosphorylation. Our results not only demonstrate the involvement of mitotic kinases in Alzheimer-type Tau phosphorylation but also indicate that Xenopus oocyte could be a useful model to identify the kinases involved in this process.

Alzheimer Disease↗

PubMed2002

Amyloid beta peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures.

The neuropathological features associated with Alzheimer's disease (AD) brain include the presence of extracellular neuritic plaques composed of amyloid beta protein (Abeta), intracellular neurofibrillary tangles containing phosphorylated tau protein and the loss of basal forebrain cholinergic neurons which innervate regions such as the hippocampus and the cortex. Studies of the pathological changes that characterize AD and several other lines of evidence indicate that Abeta accumulation in vivo may initiate phosphorylation of tau protein, which by disrupting neuronal network may trigger the process of neurodegeneration observed in AD brains. However, the underlying cause of degeneration of the basal forebrain cholinergic neurons and their association, if any, to Abeta peptides or phosphorylated tau remains mostly unknown. In the present study, using rat primary septal cultures, we have shown that aggregated Abeta peptides, in a time (18-96 h)- and concentration (0.7-60 microM)-dependent manner, induce toxicity and decrease choline acetyltransferase enzyme activity in cultured neurons. Using immunocytochemistry and immunoblotting, we have also demonstrated that Abeta treatment can significantly increase the phosphorylation of tau protein in septal cultures. At the cellular level, hyperphosphorylated tau is mostly apparent in the somatodendritic compartment of the neurons. Abeta peptide (10 microM), in addition to tau phosphorylation, also activates mitogen-activated protein kinase and glycogen synthase kinase-3beta, the two kinases which are known to be involved in the formation of hyperphosphorylated tau in the AD brain. Exposure to specific inhibitors of the mitogen-activated protein kinase (i.e. PD98059) or glycogen synthase kinase-3beta (i.e. LiCl) attenuated the hyperphosphorylation of the tau protein in cultured neurons. Given the evidence that tau phosphorylation can induce cell loss by disrupting neuronal cytoskeleton, it is likely that aggregated Abeta peptide triggers degeneration of septal neurons, including those expressing the cholinergic phenotype, by phosphorylation of the tau protein activated by mitogen-activated protein kinase and glycogen synthase kinase-3beta. These results, taken together, suggest that cultured septal cholinergic neurons are vulnerable to Abeta-mediated toxicity and tau phosphorylation may play an important role in Abeta-induced neurodegeneration.

Amyloid beta-Peptides↗