| Bradley T HymanAffiliation: Harvard University Country: USA Kara E, Marks J, Roe A, Commins C, Fan Z, Calvo Rodríguez M, et al. A flow cytometry-based in vitro assay reveals that formation of apolipoprotein E (ApoE)-amyloid beta complexes depends on ApoE isoform and cell type. J Biol Chem. 2018;293:13247-13256 pubmed publisher ..We also found subtle differences depending on the A? type and the ApoE-producing cell type. In conclusion, these results indicate that the strength of the ApoE-A? association depends on the source of A? or ApoE. .. Serrano Pozo A, Betensky R, Frosch M, Hyman B. Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease. Am J Pathol. 2016;186:375-84 pubmed publisher ..The presence of the APOEε4 allele did not affect these results. We conclude that plaques exert an increasing toxicity in the surrounding neuropil over the clinical course of AD, thereby potentially contributing to cognitive decline. .. Wegmann S, Maury E, Kirk M, Saqran L, Roe A, DeVos S, et al. Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity. EMBO J. 2015;34:3028-41 pubmed publisher ..Therefore, misfolded tau can propagate across neural systems without requisite templated misfolding, but the absence of endogenous tau markedly blunts toxicity. These results show that tau does not strictly classify as a prion protein. .. Serrano Pozo A, Qian J, Muzikansky A, Monsell S, Montine T, Frosch M, et al. Thal Amyloid Stages Do Not Significantly Impact the Correlation Between Neuropathological Change and Cognition in the Alzheimer Disease Continuum. J Neuropathol Exp Neurol. 2016;75:516-26 pubmed publisher Bennett R, Robbins A, Hu M, Cao X, Betensky R, Clark T, et al. Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease. Proc Natl Acad Sci U S A. 2018;115:E1289-E1298 pubmed publisher ..Together these data indicate that tau pathological changes in neurons can impact brain endothelial cell biology, altering the integrity of the brain's microvasculature. .. Tai H, Wang B, Serrano Pozo A, Frosch M, Spires Jones T, Hyman B. Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer's disease. Acta Neuropathol Commun. 2014;2:146 pubmed publisher ..Misfolded tau at synapses may represent early signs of neuronal degeneration, mediators of synaptotoxicity, and anatomical substrates for transmitting tauopathy, but its actual role in these processes remain to be elucidated. .. Nobuhara C, DeVos S, Commins C, Wegmann S, Moore B, Roe A, et al. Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro. Am J Pathol. 2017;187:1399-1412 pubmed publisher ..Furthermore, 6C5 slowed down the progression of tau aggregation even after uptake had begun. Our results imply that not all antibodies/epitopes are equally robust in terms of blocking tau uptake of human AD-derived tau species. .. DeVos S, Hyman B. Tau at the Crossroads between Neurotoxicity and Neuroprotection. Neuron. 2017;94:703-704 pubmed publisher ..2016) recently showed that specific tau phosphorylation is neuroprotective, phenocopying tau ablation (DeVos et al., 2017), thus highlighting the complex tau biology that underlies neurotoxicity and neuroprotection. .. Kara E, Marks J, Fan Z, Klickstein J, Roe A, Krogh K, et al. Isoform- and cell type-specific structure of apolipoprotein E lipoparticles as revealed by a novel Forster resonance energy transfer assay. J Biol Chem. 2017;292:14720-14729 pubmed publisher ..In conclusion, this study gives insights into apoE biology and establishes a robust screening system to monitor apoE conformation. ..
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