0 comments on “nanoString Webinar Thursday, 3/14/19”

nanoString Webinar Thursday, 3/14/19

A gene expression-based screening platform for mouse models of late-onset Alzheimer’s disease
When: Thursday, March 14, 9:00 a.m. PT
Speaker: Greg Carter, PhD, Associate Professor, The Jackson Laboratory
Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide, but to-date animal models of Alzheimer’s have focused on rare familial mutations. This is due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem human brain transcriptomes have identified a set of 30 gene co-expression modules associated with LOAD, providing a molecular catalog of relevant endophenotypes. Join this webinar to learn how to rapidly and reproducibly assess disease relevance of potential LOAD mouse models using gene expression analysis.
0 comments on “Identifying and ranking potential driver genes of Alzheimer’s Disease using multi-view evidence aggregation”

Identifying and ranking potential driver genes of Alzheimer’s Disease using multi-view evidence aggregation

In Mukherjee et al, we provide a generalizable framework for integration of diverse systems biology outputs to rank and identify new transcriptomic and genetic drivers of Alzheimer’s disease. This provides evidence that integration of multiple systems biology resources can provide insights into new Alzheimer’s disease loci, which can help researchers prioritize future experimental studies focusing on specific genes and pathways that are driving disease etiology.

0 comments on “MODEL-AD Presentations at ADPD Annual Conference March 26-31, 2019, Lisbon, Portugal”

MODEL-AD Presentations at ADPD Annual Conference March 26-31, 2019, Lisbon, Portugal

Wednesday, March 27th, 08:00-18:00, Exhibition Session Code A7.a

DEEP PHENOTYPING OF THE 5XFAD MOUSE MODEL USING THE MODEL-AD PIPELINE   ADPD 5xFAD poster AO
A. Oblak, H. Williams, G. Carter, S. Sukoff-Rizzo, M. Sasner, P. Territo, G. Howell, B. Lamb.
Indiana University School of Medicine, Stark Neurosciences Research Institute, Indianapolis, USA.
The Jackson Laboratory, MODEL-AD, Bar Harbor, USA.
Indiana University School of Medicine, Radiology & Imaging Sciences, Indianapolis, USA.

MODELS OF LATE ONSET ALZHEIMER’S DISEASE: THE MODEL-AD CONSORTIUM  ADPD MODEL-AD overview poster AO
A. Oblak, G. Carter, G. Howell, S. Sukoff-Rizzo, M. Sasner, P. Territo, H. Williams, B. Lamb, A. Mortazavi, M. Wood, S. Forner, G. MacGregor, A. Tenner, K. Green, F. LaFerla.
Indiana University School of Medicine, Stark Neurosciences Research institute, Indianapolis, USA.
The Jackson Laboratory, MODEL-AD, Bar Harbor, USA.
University of California Irvine, MODEL-AD, Irvine, USA.

TREM2R47H MICE SHOW A TWO-FOLD REDUCTION IN EXPRESSION AND PROTEIN LEVELS OF TREM2  ADPD Trem2R47H poster AO
A. Oblak, R. Pandey, G. Carter, H. Williams, G. Howell, M. Sasner, B. Lamb.
Indiana University School of Medicine, Stark Neurosciences Research Institute, Indianapolis, USA.
The Jackson Laboratory, MODEL-AD, Bar Harbor, USA.

EVALUATION OF CHRONIC TREATMENT WITH LEVETIRACETAM ON PHARMACOKINETCS AND PHARMACODYNAMICS IN 5XFAD MICE
S. Rizzo, S. Quinney, K. Onos, K. Keezer, L. Haynes, D. Jones, A. Masters, C. Biesdorf De Almeida, J. Meyer, J. Peters, S. Persohn, A. Bedwell, D. McKinzie, M. Sasner, G. Howell, H. Williams, A. Oblak, B. Lamb, P. Territo.
The Jackson Laboratory, Center for Biometric Analysis, Bar Harbor, USA.
Indiana University, School of Medicine, Indianapolis, USA.
The Jackson Laboratory, Institute for Mammalian Genomics, Bar Harbor, USA.

NOVEL MOUSE MODELS OF LATE-ONSET ALZHEIMER’S DISEASE EXPRESSING RISK VARIANTS AT GWAS LOCI    ADPD GWAS models poster MS
M. Sasner, A. Oblak, H. Williams, C. Preuss, G. Carter, G. Howell, B. Lamb.
The Jackson Laboratory, MODEL-AD, Bar Harbor, USA.
Indiana University, Stark Neurosciences Research Institute, Indianapolis, USA.

CHARACTERIZATION OF A NOVEL MOUSE MODEL EXPRESSING APOE4 AND TREM2*R47h FOR FURTHERING THE UNDERSTANDING OF LATE ONSET ALZHEIMER’S DISEASE    ADPD APOE4-Trem2 poster MS
M. Sasner, A. Oblak, H. Williams, S. Rizzo, P. Territo, G. Howell, B. Lamb.
The Jackson Laboratory, MODEL-AD, Bar Harbor, USA.
Indiana University, Stark Neurosciences Research Institute, Indianapolis, USA.

CHARACTERIZATION OF MOUSE MODELS BASED ON CANDIDATE GENES ASSOCIATED WITH LATE ONSET ALZHEIMER’S DISEASE   ADPD transcriptomics poster RP
R. Pandey
The Jackson Laboratory, MODEL-AD, Bar Harbor, USA

Thursday, March 28th, 17:20 – 19:20, Auditorium VIII, Session code:S28

DEVELOPING THE NEXT GENERATION OF ANIMAL MODELS OF LATE-ONSET ALZHEIMER’S DISEASE
F. Laferla
University of California Irvine, School of Biological Sciences, Irvine, USA.

HUMAN WILD-TYPE ABETA KNOCK-IN MICE AS A BASIS TO STUDY SPORADIC ALZHEIMER’S DISEASE
D. Baglietto-Vargas, L. Cai, A. Martini, L. Trujillo-Estrada, S. Forner, S. Jiang, E. Kramár, C. Nuñez-Diaz, M. Shahnawaz, M. Dina, X. Ma, C. Da Cunha, R. Ager, C. Soto, A. Gutierrez, I. Moreno-Gonzalez, G. MacGregor, K. Green, M. Wood, A. Mortazavi, A. Tenner, F. LaFerla.
University of California- Irvine, Institute for Memory Impairments and Neurological Disorders, Irvine, USA.
University of California- Irvine, Department of Developmental and Cell Biology, Irvine, USA.
University of Malaga, Department of Cell Biology- Genetic and Physiology- Faculty of Sciences- Biomedical Research Institute of Malaga IBIMA- Networking Research Center on Neurodegenerative Diseases CIBERNED, Malaga, Spain.
University of Texas Health Science Center at Houston, The Mitchell Center for Alzheimer’s Disease and Related Brain Disorders- Department of Neurology- McGovern Medical School, Houston, USA.

Friday, March 29th, 17:15 – 19:15, Auditorium VI+VII

NEXT-GENERATION MOUSE MODELS OF ALZHEIMER’S DISEASE
G. Carter
The Jackson Laboratory, MODEL-AD, Bar Harbor, USA

0 comments on “Meta-analysis of the human brain transcriptome identifies heterogeneity across human AD coexpression modules robust to sample collection and methodological approach”

Meta-analysis of the human brain transcriptome identifies heterogeneity across human AD coexpression modules robust to sample collection and methodological approach

Logsdon et al have used data from the AMP-AD consortium to identify consensus gene clusters that are differentially expressed in Alzheimer’s disease.

The MODEL-AD consortium has worked with nanoString  to develop a transcriptomics panel to assay these modules in mouse models.

We expect that this will be a rapid, cost-effective and highly reproducible approach to assess clinical relevance of novel models, to monitor disease progression, and to assay potential therapeutics.  The transcriptomics panel is now available from nanoString.

 

0 comments on “MODEL-AD Presentations at the 2018 Society for Neuroscience Meeting”

MODEL-AD Presentations at the 2018 Society for Neuroscience Meeting

Monday, November 5, 1:30pm – 4pm
Session 345: Global Efforts to Build More Predictive Animal Models of Neurodegenerative Disease
Chair: Bruce T. Lamb, PhD, Indiana University School of Medicine
Co-Chair: Rudolph E. Tanzi, PhD, Massachusetts General Hospital, Harvard Medical School
Location: SDCC 6B 2:45-3:20PM
345.04 Bruce Lamb: Novel insights into Alzheimer’s disease through the MODEL-AD consortium

Nanosymposium 267: Alzheimer’s Disease: Neuroinflammation and Immune Actions
Location: SDCC 24
10:15-10:30 267.10 Kristen Onos: Genetic diversity is a significant driver of amyloid-induced neuroinflammation and neurodegeneration in APP/PS1 mice

Tuesday November 6
Poster Session 466: Alzheimer’s Disease and Other Dementias: Genetic Analysis and Omics Approaches
Systems biology-based method to identify and prioritize Alzheimer’s disease candidate driver genes
S. Mukherjee, T. M. Perumal, K. Daily, S. Sieberts, L. Omberg, C. Preuss, G. Carter, L. Mangravite, B. Logsdon
Board F23, #462.20 presented 11:00-12:00am

Poster Session 467: Alzheimer’s Disease and Other Dementias: Therapeutic Strategies: Preclinical Animal Models II
Novel models of late-onset Alzheimer’s disease
Mike Sasner for the MODEL-AD Center   Sasner SfN 2018 GWAS poster final
Board G8, #467.01 presented 8:00-9:00am

hAb-KI: A knock-in mouse model for sporadic Alzheimer’s disease
Stefania Forner for the MODEL-AD Center
Board G9, #467.02, presented 9:00-10:00am

MODEL-AD: Late-onset Alzheimer’s disease models
Adrian Oblak for the MODEL-AD Center   Oblak OverviewFINAL
Board G10, #467.03 presented 10:00-11:00am

Preclinical screening strategy of the MODEL-AD consortium: Evaluation of the pharmacokinetics and pharmacodynamics of treatment with Levetiracetam
Stacey Rizzo for the MODEL-AD Center   Rizzo et al SfN PTC MODELAD Poster – 20181029 vPRT_sjsr_FINAL
Board G11, #467.04 presented 11:00am-noon

Translational genetic and genomic analyses of new mouse models of Alzheimer’s disease
Greg Carter for the MODEL-AD Center   Carter_SFN_2018
Board G12, #467.05 presented 8:00-9:00am

MODEL-AD: Standardized characterization of familial Alzheimer’s disease models (5xFAD, 3Tg-AD, APP/PS1, and hTau)
Gareth Howell for the MODEL-AD Center   Howell FAD SfN MODEL-AD poster
Board G13, #467.06 presented 9:00-10:00am

Wednesday, November 7, 1:00 PM – 3:15 PM
Nanosymposium 713: Alzheimer’s Disease and Other Dementias: Abeta: Pathologic Mechanisms
Location: SDCC 33

1:45-2:00 713.04 David Baglietto-Vargas hAb-KI mice: A novel tool for investigating risk factors in sporadic Alzheimer’s cases

 

 

 

 

0 comments on “The Trem2 R47H Alzheimer’s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans.”

The Trem2 R47H Alzheimer’s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans.

A recent publication from the lab of Christian Haass has shown altered splicing of mouse Trem2 that is dependent upon the presence of the R47H mutation and leads to a cryptic splice site in exon 2 and a deletion of 119 nucleotides.

The MODEL-AD project has similar data demonstrating the cryptic splice site.  We are currently using Western blots and whole-brain transcriptomic analysis to assay mutant protein levels.  For now, we argue that the conclusion that “functional data derived from Trem2*R47H knock-in mice cannot be translated to humans” put forward in this paper may be premature because full-length transcripts are generated in Trem2*R47H homozygotes, albeit at reduced levels.

In parallel, we are considering alternative strategies to create Trem2 alleles to model late-onset AD.

AlzForum story

Article in PubMed

0 comments on “MODEL-AD Mini-Symposium 5/22/17”

MODEL-AD Mini-Symposium 5/22/17

The Jackson Laboratory hosted a MODEL-AD Mini-Symposium on Monday, May 22, 2017 from 2:15 to 5:15 p.m in the LCC Auditorium at our Bar Harbor, Maine campus. The symposium included updates from Alzheimer’s Disease experts and was followed by a poster session. For more information, please contact Mike Sasner (mike.sasner@jax.org).

Agenda:

  • 2:15 pm: Welcome – Gareth Howell, Ph.D., Associate Professor, The Jackson Laboratory
  • 2:30 pm: “Unraveling the Role of TREM2 in Alzheimer’s Disease Pathogenesis” Bruce Lamb, Ph.D., Roberts Family Chair in Alzheimer’s Disease Research, Executive Director, Stark Neurosciences Research Institute, Indiana University School of Medicine
  • 2:45 pm: “Research at the Toronto Dementia Research Alliance” – Barry Greenberg, Ph.D., Director of Strategy, Toronto Dementia Research Alliance, University Health Network, Toronto
  • 3:00 pm: “Preclinical Development of a CNS-active, Isoform-selective, p38alpha MAPK Inhibitor for Alzheimer’s Disease” – Linda Van Eldik, Ph.D., Director, Alzheimer’s Disease Center, University of Kentucky, Co-Director, Kentucky Neuroscience Institute, Vernon Smith Endowed Chair in Alzheimer’s Research
  • 3:15 pm: “Systems Genetics Analysis of Resilience to Alzheimer’s Disease”  Catherine Kaczorowski, Ph.D., Assistant Professor, The Jackson Laboratory
  • 3:30 pm: “Appropriate Use of Animal Models to Translate Aβ Lowering Effects of BACE1 Inhibition to the Clinic” – Dave McKinzie, Ph.D., Research Fellow & Head of In Vivo Pharmacology, Eli Lilly
  • 3:45 pm: “MODEL-AD: Creating the Next Generation of Animal Models for Alzheimer’s Disease” – Greg Carter, Ph.D., Associate Professor, The Jackson Laboratory
  • 4:00 pm: Collaborative Frameworks and Open Science: New Frontiers in Systems Biology” – Ben Logsdon, Ph.D., Senior Scientist, Sage Bionetworks
  • 4:15 pm: Poster session with wine and cheese
  • 5:15 pm: Adjourn