Tangle Formation (tangle + formation)

Distribution by Scientific Domains


Selected Abstracts


Glutamatergic systems in Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue S1 2003
Paul T. Francis
Abstract Glutamate is the major transmitter of the brain and is involved in all aspects of cognitive function since it is the transmitter of cortical and hippocampal pyramidal neurones. Furthermore, glutamate and glutamate receptors are involved in long-term potentiation, a process believed to underlie learning and memory. Histological studies indicate loss of pyramidal neurones and their synapses in Alzheimer's disease (AD), this together with biochemical evidence suggests presynaptic (and postsynaptic) glutamatergic hypoactivity. This represents a ,double blow' as the activity of glutamatergic neurones is heavily influenced by the cholinergic system, which is also dysfunctional in AD. The clinical relevance of these changes is emphasised because glutamatergic and cholinergic dysfunction are strong correlates of cognitive decline in AD. The mechanism by which glutamatergic (and cholinergic) cells die is likely to be a combination of necrosis and apoptosis caused by a range of factors which include tangle formation and the effects of too much and too little glutamatergic neurotransmission. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Chronic lithium administration to FTDP-17 tau and GSK-3, overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert

JOURNAL OF NEUROCHEMISTRY, Issue 6 2006
Tobias Engel
Abstract Glycogen synthase kinase-3 (GSK-3) has been proposed as the main kinase able to aberrantly phosphorylate tau in Alzheimer's disease (AD) and related tauopathies, raising the possibility of designing novel therapeutic interventions for AD based on GSK-3 inhibition. Lithium, a widely used drug for affective disorders, inhibits GSK-3 at therapeutically relevant concentrations. Therefore, it was of great interest to test the possible protective effects of lithium in an AD animal model based on GSK-3 overexpression. We had previously generated a double transgenic model, overexpressing GSK-3, in a conditional manner, using the Tet-off system and tau protein carrying a triple FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) mutation. This transgenic line shows tau hyperphosphorylation in hippocampal neurones accompanied by neurofibrillary tangles (NFTs). We used this transgenic model to address two issues: first, whether chronic lithium treatment is able to prevent the formation of aberrant tau aggregates that result from the overexpression of FTDP-17 tau and GSK-3,; second, whether lithium is able to change back already formed NFTs in aged animals. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Furthermore, it is still possible to partially reverse tau pathology in advanced stages of the disease, although NFT-like structures cannot be changed. The same results were obtained after shut-down of GSK-3, overexpression, supporting the possibility that GSK-3 inhibition is not sufficient to reverse NFT-like aggregates. [source]


Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: in vitro evidence and implications for tangle formation in vivo

JOURNAL OF NEUROCHEMISTRY, Issue 4 2006
Angela L. Guillozet-Bongaarts
Abstract The tangles of Alzheimer's disease (AD) are comprised of the tau protein displaying numerous alterations, including phosphorylation at serine 422 (S422) and truncation at aspartic acid 421 (D421). Truncation at the latter site appears to result from activation of caspases, a class of proteases that cleave specifically at aspartic acid residues. It has been proposed that phosphorylation at or near caspase cleavage sites could regulate the ability of the protease to cleave at those sites. Here, we use tau pseudophosphorylated at S422 (S422E) to examine the effects of tau phosphorylation on its cleavage by caspase 3. We find that S422E tau is more resistant to proteolysis by caspase 3 than non-pseudophosphorylated tau. Additionally, we use antibodies directed against the phosphorylation site and against the truncation epitope to assess the presence of these epitopes in neurofibrillary tangles in the aged human brain. We show that phosphorylation precedes truncation during tangle maturation. Moreover, the distribution of the two epitopes suggests that a significant length of time (perhaps as much as two decades) elapses between S422 phosphorylation and cleavage at D421. We further conclude that tau phosphorylation at S422 may be a protective mechanism that inhibits cleavage in vivo. [source]


Diagnostic clues and more from photographs

NEUROPATHOLOGY, Issue 1 2007
Asao Hirano
During over 50 years of the first author's career in neuropathology at Montefiore Medical Center in New York, we have come across certain interesting neuropathological findings. In this communication, some photographs showing macroscopic, microscopic and electron microscopic significant findings are selected to illustrate usefulness not only for the diagnosis but also for understanding of the nervous system. The six topics presented in this paper are: (i) unattached presynaptic terminals in cerebellar neuroblastoma; (ii) neurofibrillary tangle formation in the nucleus basalis of Meynert ipsilateral to a massive cerebral infarct; (iii) orderly arrangement of tumor cells in leptomeningeal carcinomatosis; (iv) interface between craniopharyngioma and brain tissue; (v) neurofibrillary tangles and Lewy bodies in a single neuron; and (vi) Cu/Zn superoxide dismutase positive Lewy body-like hyaline inclusions in anterior horn cells in familial motor neuron diseases. Analyses of these findings are presented for an educational purpose. [source]