Beta Amyloid Peptide: CONFERENCE COVERAGE: Tau2020 Global Conference

A new meeting in the calendar, Tau2020, covered the biology and pathology of all tauopathies, both primary and secondary. Some of the 650 attendees saw it as an inflection point in tau research, getting researchers to think more broadly and bringing their collective knowledge to bear on a common problem. Highlights included a new staging scheme for tau progression in AD, new ligands for primary tauopathies, cryoEM structures for α-synuclein, and a receptor that facilitates spread of mutant tau in mouse models. 

This article originally appeared in the " https://www.alzforum.org/news/conference-coverage/tau2020-global-conference  " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : An electrochemical immunosensor using gold nanoparticles-PAMAM-nanostructured screen-printed carbon electrodes for tau protein determination in plasma and brain tissues from Alzheimer patients

Abstract

This work reports a new sensitive strategy for the determination of tau protein, a hallmark of Alzheimer's disease (AD), involving a sandwich immunoassay and amperometric detection at disposable screen-printed carbon electrodes (SPCEs) modified with a gold nanoparticles-poly(amidoamine) (PAMAM) dendrimer nanocomposite (3D-Au-PAMAM) covalently immobilized onto electrografted p-aminobenzoic acid (p-ABA). The capture antibody (CAb) was immobilized by crosslinking with glutaraldehyde (GA) on the amino groups of the 3D-Au-PAMAM-p-ABA-SPCE, where tau protein was sandwiched with a secondary antibody labeled with horseradish peroxidase (HRP-DAb). Amperometry at -200 mV (vs the Ag pseudo-reference electrode) upon the addition of hydroquinone (HQ) as electron transfer mediator and H2O2 as the enzyme substrate was used to detect the immunocomplex formation. The great analytical performance of the immunosensor in terms of selectivity and low limit of detection (LOD) (1.7 pg mL-1) allowed the direct determination of the target protein in raw plasma samples and in brain tissue extracts from healthy individuals and post mortem diagnosed AD patients, using a simple and fast protocol.

Keywords: Amperometric sandwich immunoassay; Brain tissue; Dendrimer nanocomposite; Raw plasma; Screen-printed electrode; Tau protein.

Copyright © 2020 Elsevier B.V. All rights reserved.

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/32579671/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Beta Amyloid Peptide: Research Paper : Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline

Abstract

Objective: To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois.

Methods: We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the "Neuro first" group had neurological manifestations upon initial assessment, and the "COVID first" group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups.

Results: A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The "COVID-19 first" group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025).

Conclusion: Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

Published by Elsevier B.V.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/32579671/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Beta Amyloid Peptide: Research Paper : Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer's disease model

TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy.

© 2020 Wang et al.

Conflict of interest statement

Disclosures: M. Mustafa, S.V. Salazar, P. Kong, H. Long, M. Ward, O. Siddiqui, R. Paul, A. Ibrahim, H. Rhinn, I. Tassi, A. Rosenthal, and T. Schwabe reported "other" from Alector, Inc. during the conduct of the study. The authors are employees of Alector LLC and may have an equity interest in Alector, Inc. Alector and AbbVie are parties to an agreement relating to the development and commercialization of AL002. M. Colonna reported "other" from Alector and grants from Alector, Amgen, and Ono during the conduct of the study. In addition, Alector LLC has pending patent applications and M. Colonna has a patent to TREM2 pending. No other disclosures were reported.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/32579671/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Beta Amyloid Peptide: JOBS: Postdoctoral Fellow

Employer

Center for Alzheimer's and Neurodegenerative Diseases at University of Texas Southwestern Medical Center

Location

Dallas, Texas

Principal Investigator

Rachel Bailey

Contact

Interested applicants should contact Dr. Bailey at Rachel.Bailey@UTSouthwestern.edu and provide a brief cover letter, a CV, and contact info for three references.

Description

A postdoctoral training position is immediately available in the laboratory of Dr. Rachel Bailey in the Center for Alzheimer's & Neurodegenerative Diseases at UT Southwestern Medical Center to study research using adeno-associated virus (AAV) gene therapy for the treatment of neurodegenerative diseases. The laboratory has several gene therapy projects with the eventual goal of translating research to a Phase I clinical trial. The position will perform specialized research experiments in cultured cells and small animals.

UT Southwestern Medical Center is an Affirmative Action/Equal Opportunity Employer. Women, minorities, veterans and individuals with disabilities are encouraged to apply. Information on UT's postdoctoral training program and benefits can be found in its postdoc handbook or at http://www.utsouthwestern.edu/postdocs.

Requirements

Candidates must hold a Ph.D. degree. Interested candidates must have 1) a strong background in biochemistry, cell biology, molecular biology, or a related discipline, 2) publication and grant writing record, 3) scientific curiosity and the desire and ability to work independently.

Experience with disease models and genomic approaches (i.e. RNA-seq) are a plus.

Beta Amyloid Peptide: CONFERENCE COVERAGE: AAT-AD/PD™ 2020 Conference: Advances in Alzheimer's and Parkinson's Therapies

Caught amid COVID-19, the organizers of this meeting decided on March 10, 2020, to switch to a virtual format. It offered prerecorded lectures and e-posters, as well as livestreamed discussions, "Meet-the-Professor" audio chats, and a virtual exhibit hall. New data included widely anticipated results of the DIAN-TU clinical trial of solanezumab and gantenerumab, and of robust phospho-tau plasma tests. The online stream also brought new data on a range of trials against tau, α-synuclein, and other targets in age-related neurodegenerative disease, and on pathogenesis and other topics.    

Beta Amyloid Peptide: Research Paper : Transfer of pathological α-synuclein from neurons to astrocytes via exosomes causes inflammatory responses after METH exposure

Methamphetamine (METH) is a highly addictive psychostimulant drug whose abuse can cause many health complications. Our previous studies have shown that METH exposure increases α-synuclein (α-syn) expression. Recently, it was shown that α-syn could be transferred from neurons to astrocytes via exosomes. However, the specific role of astrocytes in α-syn pathology involved in METH neurotoxicity remains unclear. The objective of this study was to determine whether exosomes derived from METH-treated neurons contain pathological α-syn and test the hypothesis that exosomes can transfer pathological α-syn from neurons to astrocytes. To this end, using animal and cell line coculture models, we show that exosomes isolated from METH-treated SH-SY5Y cells contained pathological α-syn. Furthermore, the addition of METH exosomes to the medium of primary cultured astrocytes induced α-syn aggregation and inflammatory responses in astrocytes. Then, we evaluated changes in nuclear receptor related 1 protein (Nurr1) expression and the levels of inflammatory cytokines in primary cultured astrocytes exposed to METH or α-syn. We found that METH or α-syn exposure decreased Nurr1 expression and increased proinflammatory cytokine expression in astrocytes. Our results indicate that α-syn can be transferred from neuronal cells to astrocytes through exosomes. When internalized α-syn accumulated in astrocytes, the cells produced inflammatory responses. Nurr1 may play a crucial role in this process and could be a therapeutic target for inflammatory damage caused by METH.

Keywords: Exosomes; Inflammation; Methamphetamine; Nurr1; α-synuclein.

Copyright © 2020 Elsevier B.V. All rights reserved.

Beta Amyloid Peptide: Grant: Preclinical Development of Novel Therapeutics Targeting Aging Mechanisms (SBIR U44 Clinical Trial Not Allowed)

This Funding Opportunity Announcement (FOA) utilizes the SBIR cooperative agreement (U44) activity code to support the preclinical development of emerging therapeutics targeting fundamental mechanisms of aging (e.g., inflammation, cell senescence, proteostasis). This includes the translation of a broad range of potential geroscience-based therapies, such as new classes of compounds (e.g., senolytics), biologics, stem/progenitor cell-based therapies, repositioning of existing investigational drugs, and repurposing of Food and Drug Administration (FDA)-approved drugs for the treatment and prevention of clinical conditions related to aging and common in the aged. Examples of translational research activities eligible under this FOA include target validation, optimization of lead compounds, pharmacokinetics and drug disposition studies, and preclinical safety/toxicology studies. NIA encourages the submission of applications which involve translational research activities across all stages of preclinical drug development. The development and validation of new methodologies (e.g., organoids, in silico approaches) necessary to advance preclinical development of a given therapeutic are also allowed. While the use of relevant human in vitro systems (e.g., organoids, microphysiological systems (MPS), induced pluripotent stem cells (PSCs)) is strongly encouraged in the preclinical development process, the conduct of first-in-human (FIH) studies and/or early phase clinical trials are outside the scope of this FOA.

Applicants must include a Target Product Profile (TPP) based on FDA guidance in their applications. In addition, U44 awardees will be required to convene periodic meetings with the FDA to discuss any necessary modifications to the TPP based on research progress or to meet specific regulatory requirements (e.g., pre-IND meeting).

Preclinical development of new drugs for Alzheimer's disease and its related dementias (AD/ADRD) are outside the scope of this FOA, as several other NIA FOAs are available for this purpose. Information on current NIA FOAs on AD/ADRD is available at https://www.nia.nih.gov/ad-foas.

Beta amyloid Peptide Administrative Supplement for Research on Dietary Supplements (Admin Supp-Clinical Trial Not Allowed) (PA-20-227)

Administrative Supplement for Research on Dietary Supplements (Admin Supp-Clinical Trial Not Allowed) (PA-20-227)

Sponsor: National Institutes of Health

Award: ODS intends to commit $3 million in 2021 to fund 20 awards, $3 million in 2022 to fund 20 awards, and $3 million in 2023 to fund 20 awards.

Due Date: October 15, 2020; January 15, 2021; April 15, 2021; October 15, 2021; January 15, 2022; April 15, 2022; October 15, 2022; January 15, 2023; April 15, 2023, by 5 p.m. local time of applicant organization.

https://grants.nih.gov/grants/guide/pa-files/PA-20-227.html

Beta Amyloid peptide Administrative Supplement for Research on Dietary Supplements (Admin Supp-Clinical Trial Not Allowed) (PA-20-227)

Administrative Supplement for Research on Dietary Supplements (Admin Supp-Clinical Trial Not Allowed) (PA-20-227)

Sponsor: National Institutes of Health

Award: ODS intends to commit $3 million in 2021 to fund 20 awards, $3 million in 2022 to fund 20 awards, and $3 million in 2023 to fund 20 awards.

Due Date: October 15, 2020; January 15, 2021; April 15, 2021; October 15, 2021; January 15, 2022; April 15, 2022; October 15, 2022; January 15, 2023; April 15, 2023, by 5 p.m. local time of applicant organization.

https://grants.nih.gov/grants/guide/pa-files/PA-20-227.html