Your browser doesn't support javascript.
loading
Genetic diversity promotes resilience in a mouse model of Alzheimer's disease.
Soni, Neelakshi; Hohsfield, Lindsay A; Tran, Kristine M; Kawauchi, Shimako; Walker, Amber; Javonillo, Dominic; Phan, Jimmy; Matheos, Dina; Da Cunha, Celia; Uyar, Asli; Milinkeviciute, Giedre; Gomez-Arboledas, Angela; Tran, Katelynn; Kaczorowski, Catherine C; Wood, Marcelo A; Tenner, Andrea J; LaFerla, Frank M; Carter, Gregory W; Mortazavi, Ali; Swarup, Vivek; MacGregor, Grant R; Green, Kim N.
Afiliación
  • Soni N; Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
  • Hohsfield LA; Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
  • Tran KM; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Kawauchi S; Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
  • Walker A; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Javonillo D; Transgenic Mouse Facility, ULAR, Office of Research, University of California, Irvine, California, USA.
  • Phan J; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Matheos D; Transgenic Mouse Facility, ULAR, Office of Research, University of California, Irvine, California, USA.
  • Da Cunha C; Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
  • Uyar A; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Milinkeviciute G; Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
  • Gomez-Arboledas A; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Tran K; The Jackson Laboratory, Bar Harbor, Maine, USA.
  • Kaczorowski CC; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Wood MA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Tenner AJ; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • LaFerla FM; Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
  • Carter GW; Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
  • Mortazavi A; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Swarup V; Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
  • MacGregor GR; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.
  • Green KN; Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.
Alzheimers Dement ; 20(4): 2794-2816, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38426371
ABSTRACT

INTRODUCTION:

Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial etiology, including genetic factors that play a significant role in disease risk and resilience. However, the role of genetic diversity in preclinical AD studies has received limited attention.

METHODS:

We crossed five Collaborative Cross strains with 5xFAD C57BL/6J female mice to generate F1 mice with and without the 5xFAD transgene. Amyloid plaque pathology, microglial and astrocytic responses, neurofilament light chain levels, and gene expression were assessed at various ages.

RESULTS:

Genetic diversity significantly impacts AD-related pathology. Hybrid strains showed resistance to amyloid plaque formation and neuronal damage. Transcriptome diversity was maintained across ages and sexes, with observable strain-specific variations in AD-related phenotypes. Comparative gene expression analysis indicated correlations between mouse strains and human AD.

DISCUSSION:

Increasing genetic diversity promotes resilience to AD-related pathogenesis, relative to an inbred C57BL/6J background, reinforcing the importance of genetic diversity in uncovering resilience in the development of AD. HIGHLIGHTS Genetic diversity's impact on AD in mice was explored. Diverse F1 mouse strains were used for AD study, via the Collaborative Cross. Strain-specific variations in AD pathology, glia, and transcription were found. Strains resilient to plaque formation and plasma neurofilament light chain (NfL) increases were identified. Correlations with human AD transcriptomics were observed.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Resiliencia Psicológica / Enfermedad de Alzheimer Límite: Animals / Female / Humans Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Resiliencia Psicológica / Enfermedad de Alzheimer Límite: Animals / Female / Humans Idioma: En Año: 2024 Tipo del documento: Article