Soluble forms of tau are toxic in Alzheimer's disease

Accumulation of neurofibrillary tangles (NFT), intracellular inclusions of fibrillar forms of tau, is a hallmark of Alzheimer Disease. NFT have been considered causative of neuronal death, however, recent evidence challenges this idea. Other species of tau, such as soluble misfolded, hyperphosphorylated, and mislocalized forms, are now being implicated as toxic. Here we review the data supporting soluble tau as toxic to neurons and synapses in the brain and the implications of these data for development of therapeutic strategies for Alzheimer’s disease and other tauopathies

Complexes of syndapin II with dynamin II promote vesicle formation at the trans-Golgi network

The role of dynamin and so-called accessory proteins in endocytosis is well established. However, molecular details of the function(s) of dynamin II at the Golgi are largely unclear. We demonstrate that the ubiquitously expressed syndapin II isoform interacts with the proline-rich domain (PRD) of dynamin II through its Src-homology 3 (SH3) domain. Co-immunoprecipitation of endogenous syndapin II and dynamin II, and successful reconstitutions of such complexes at membranes in COS-7 cells, show the in vivo relevance of the interaction. Syndapin II can associate with Golgi membranes and this association increases upon Golgi exit block. Brefeldin A treatment clearly shows that the observed perinuclear localization of syndapin II co-localizing with syntaxin 6 reflects the Golgi complex and that it requires functional integrity of the Golgi. Syndapins are crucial for Golgi vesicle formation because antisyndapin antibodies, used either in in vitro reconstitutions or in living cells, inhibited this process. Both types of assays additionally revealed the essential role of syndapin II SH3 interactions with the dynamin II PRD in vesicle formation. An excess of the syndapin SH3 domain strongly inhibited budding from Golgi membranes in vitro. Likewise, overexpression of the syndapin SH3 domain or of a dynamin II variant incapable of associating with syndapin II (dynamin IIΔPRD) impaired trafficking of vesicular stomatitis virus glycoprotein (VSVG)-GFP in vivo. By contrast, full-length syndapin II-I had no negative effect, and instead promoted VSVG-GFP export from the Golgi. Importantly, a cytosolic fraction containing endogenous syndapin-dynamin complexes was sufficient to promote vesicle formation from Golgi membranes in a syndapin-dependent manner. Thus, syndapin-dynamin complexes are crucial and sufficient to promote vesicle formation from the trans-Golgi network

Advanced multicentric lymphoma in a Belgian Draft Horse mare

A 15-year old draft horse mare was presented to the University Clinic for evaluation of lethargy, anorexia, ptyalism, weight loss and ventral oedema. Clinical examination and rectal palpation revealed generalised lymphadenopathy and numerous firm subcutaneous and abdominal masses of various sizes. Transcutaneous ultrasonography revealed significant bilateral pleural fluid accumulation and a single hypoechoic structure in the abdomen lateral to the liver. Blood analysis showed several abnormalities including a marked leucocytosis with an increased number of segmented neutrophils, atypical lymphocytes and monocytosis, suggestive of leukaemic lymphoma. A significant hyperproteinaemia with a hypoalbuminemia and a monoclonal gammopathy was identified. At necropsy myriad masses presented through the whole body. Histology confirmed the suspicion of lymphoma, which was classified as a T-cell rich B-cell multicentric lymphoma. This article describes the clinical and pathologic findings of this case of leukaemic lymphoma

Advanced multicentric lymphoma in a Belgian Draft Horse mare

A 15-year old draft horse mare was presented to the University Clinic for evaluation of lethargy, anorexia, ptyalism, weight loss and ventral oedema. Clinical examination and rectal palpation revealed generalised lymphadenopathy and numerous firm subcutaneous and abdominal masses of various sizes. Transcutaneous ultrasonography revealed significant bilateral pleural fluid accumulation and a single hypoechoic structure in the abdomen lateral to the liver. Blood analysis showed several abnormalities including a marked leucocytosis with an increased number of segmented neutrophils, atypical lymphocytes and monocytosis, suggestive of leukaemic lymphoma. A significant hyperproteinaemia with a hypoalbuminemia and a monoclonal gammopathy was identified. At necropsy myriad masses presented through the whole body. Histology confirmed the suspicion of lymphoma, which was classified as a T-cell rich B-cell multicentric lymphoma. This article describes the clinical and pathologic findings of this case of leukaemic lymphoma