Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer's disease

Stefania Forner; Shimako Kawauchi; Gabriela Balderrama-Gutierrez; Enikö A Kramár; Dina P Matheos; Jimmy Phan; Dominic I Javonillo; Kristine M Tran; Edna Hingco; Celia da Cunha; Narges Rezaie; Joshua A Alcantara; David Baglietto-Vargas; Camden Jansen; Jonathan Neumann; Marcelo A Wood; Grant R MacGregor; Ali Mortazavi; Andrea J Tenner; Frank M LaFerla; Kim N Green

doi:10.1038/s41597-021-01054-y

Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer's disease

Sci Data. 2021 Oct 15;8(1):270. doi: 10.1038/s41597-021-01054-y.

Authors

Stefania Forner^#¹, Shimako Kawauchi^#², Gabriela Balderrama-Gutierrez^{3

4}, Enikö A Kramár⁵, Dina P Matheos⁵, Jimmy Phan¹, Dominic I Javonillo¹, Kristine M Tran¹, Edna Hingco¹, Celia da Cunha¹, Narges Rezaie^{3

4}, Joshua A Alcantara², David Baglietto-Vargas¹, Camden Jansen^{3

4}, Jonathan Neumann², Marcelo A Wood⁵, Grant R MacGregor^{2

3}, Ali Mortazavi^{3

4}, Andrea J Tenner^{1

5

6

7}, Frank M LaFerla^{1

5}, Kim N Green^{8

9}

Affiliations

¹ Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, CA, 92697, USA.
² Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, University of California, Irvine, CA, 92697, USA.
³ Department of Developmental and Cell Biology, University of California, Irvine, CA, 92697, USA.
⁴ Center for Complex Biological Systems, University of California, Irvine, CA, 92697, USA.
⁵ Department of Neurobiology and Behavior, University of California, Irvine, CA, 92697, USA.
⁶ Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA.
⁷ Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, 92697, USA.
⁸ Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, CA, 92697, USA. kngreen@uci.edu.
⁹ Department of Neurobiology and Behavior, University of California, Irvine, CA, 92697, USA. kngreen@uci.edu.

^# Contributed equally.

Abstract

Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions and therapeutics. For disorders such as Alzheimer's disease in which numerous models are being generated, a challenging first step is to identify the most appropriate model and age to effectively evaluate new therapeutic approaches. Here we conducted a detailed phenotypic characterization of the 5xFAD model on a congenic C57BL/6 J strain background, across its lifespan - including a seldomly analyzed 18-month old time point to provide temporally correlated phenotyping of this model and a template for characterization of new models of LOAD as they are generated. This comprehensive analysis included quantification of plaque burden, Aβ biochemical levels, and neuropathology, neurophysiological measurements and behavioral and cognitive assessments, and evaluation of microglia, astrocytes, and neurons. Analysis of transcriptional changes was conducted using bulk-tissue generated RNA-seq data from microdissected cortices and hippocampi as a function of aging, which can be explored at the MODEL-AD Explorer and AD Knowledge Portal. This deep-phenotyping pipeline identified novel aspects of age-related pathology in the 5xFAD model.

Publication types

Dataset
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / genetics*
Animals
Behavior, Animal
Disease Models, Animal*
Hippocampus
Long-Term Potentiation
Mice
Mice, Inbred C57BL
Phenotype*
RNA-Seq
Synaptic Transmission

Abstract

Publication types

MeSH terms

Grants and funding