Soluble tau aggregates, not large fibrils, are the toxic species that display seeding and cross‐seeding behavior
Gaurav Ghag,Nemil Bhatt,Daniel V. Cantu,Marcos J. Guerrero-Muñoz,Anna Ellsworth,Urmi Sengupta,Rakez Kayed +6 more
TLDR
The results corroborate the previous studies showing that sonication of prion and Aβ fibrils leads to the formation of toxic, soluble aggregates and show that the oligomeric forms are the most toxic species although it is unclear how sonication causes oligomer formation.Abstract:
Several studies have proposed that fibrillary aggregates of tau and other amyloidogenic proteins are neurotoxic and result in numerous neurodegenerative diseases. However, these studies usually involve sonication or extrusion through needles before experimentation. As a consequence, these methods may fragment large aggregates producing a mixture of aggregated species rather than intact fibrils. Therefore, the results of these experiments may be reflective of other amyloidogenic species, such as oligomers and/or protofibrils/short fibrils. To investigate the effects of sonication on the aggregation of tau and other amyloidogenic proteins, fibrils were prepared and well characterized, then sonicated and evaluated by various biochemical and biophysical methods to identify the aggregated species present. We found that indeed a mixture of aggregated species was present along with short fibrils indicating that sonication leads to impure fibril samples and should be analyzed with caution. Our results corroborate the previous studies showing that sonication of prion and Aβ fibrils leads to the formation of toxic, soluble aggregates. We also show that the oligomeric forms are the most toxic species although it is unclear how sonication causes oligomer formation. Recent results suggest that these small toxic oligomers produced by sonication, rather than the stable fibrillar structures, are prion-like in nature displaying seeding and cross-seeding behavior.read more
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The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease
Martí Colom-Cadena,Tara L. Spires-Jones,Henrik Zetterberg,Kaj Blennow,Kaj Blennow,Anthony O. Caggiano,Steven T. DeKosky,Howard Fillit,John Harrison,Lon S. Schneider,P. Scheltens,Willem de Haan,Willem de Haan,Michael Grundman,Christopher H. van Dyck,Nicholas J. Izzo,Susan M. Catalano +16 more
TL;DR: A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD and hold promise both for use in diagnostics and in the measurement of therapeutic successes.
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Effects of in vivo conditions on amyloid aggregation.
Michael C. Owen,David Gnutt,Mimi Gao,Sebastian K.T.S. Wärmländer,Jüri Jarvet,Astrid Gräslund,Roland Winter,Simon Ebbinghaus,Birgit Strodel,Birgit Strodel +9 more
TL;DR: The aim of this review is to document the progress in the research onAmyloid formation from a physicochemical perspective with a special focus on the physiological factors influencing the aggregation of the amyloid-β peptide, the islet amyloids polypeptide, α-synuclein, and the hungingtin protein.
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The Pathobiology of TDP-43 C-Terminal Fragments in ALS and FTLD
TL;DR: It is concluded that although TDP-43 CTFs are a hallmark of T DP-43-related neurodegeneration in the brain, they are not a primary cause of ALS or FTLD and largely fails to induce motor or behavioral dysfunction reminiscent of human disease.
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Alzheimer’s disease brain-derived extracellular vesicles spread tau pathology in interneurons
Zhi Ruan,Dhruba Pathak,Srinidhi Venkatesan Kalavai,Asuka Yoshii-Kitahara,Satoshi Muraoka,Nemil Bhatt,Kayo Takamatsu-Yukawa,Jianqiao Hu,Yuzhi Wang,Samuel Hersh,Maria Ericsson,Santhi Gorantla,Howard E. Gendelman,Rakez Kayed,Seiko Ikezu,Jennifer I. Luebke,Tsuneya Ikezu +16 more
TL;DR: It is shown that brain-derived extracellular vesicles from human donors with Alzheimer’s disease propagate tau more efficiently when injected into the mouse hippocampus than oligomeric or fibrillary tau from the same donors.
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Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.
Eftychia Vasili,Antonio Dominguez-Meijide,Tiago F. Outeiro,Tiago F. Outeiro,Tiago F. Outeiro +4 more
TL;DR: The mechanisms involved, the similarities and differences between the spreading of the two proteins and that of the prion protein, and the different cell and animal models used for studying these processes are discussed.
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