Genetic diversity promotes resilience in a mouse model of Alzheimer's disease

被引：5

作者：

Soni, Neelakshi ^{[1
]}

Hohsfield, Lindsay A. ^{[1
,2
]}

Tran, Kristine M. ^{[1
]}

Kawauchi, Shimako ^{[2
,3
]}

Walker, Amber ^{[2
,3
]}

Javonillo, Dominic ^{[1
]}

Phan, Jimmy ^{[2
]}

Matheos, Dina ^{[1
]}

Da Cunha, Celia ^{[2
]}

Uyar, Asli ^{[4
]}

Milinkeviciute, Giedre ^{[2
]}

Gomez-Arboledas, Angela ^{[2
]}

Tran, Katelynn ^{[2
]}

Kaczorowski, Catherine C. ^{[5
]}

Wood, Marcelo A. ^{[1
,2
]}

Tenner, Andrea J. ^{[1
,2
,6
,7
]}

LaFerla, Frank M. ^{[1
,2
]}

Carter, Gregory . ^{[4
]}

Mortazavi, Ali ^{[2
,8
,9
]}

Swarup, Vivek ^{[1
,2
]}

MacGregor, Grant R. ^{[3
,8
]}

Green, Kim N. ^{[1
,2
]}

机构：

[1] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA

[2] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA USA

[3] Univ Calif Irvine, Transgen Mouse Facil, ULAR, Res Off, Irvine, CA USA

[4] Jackson Lab, Bar Harbor, ME USA

[5] Univ Michigan, Dept Neurol, Ann Arbor, MI USA

[6] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA USA

[7] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA

[8] Univ Calif Irvine, Dept Dev & Cellular Biol, Irvine, CA USA

[9] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA USA

来源：

ALZHEIMERS & DEMENTIA | 2024年 / 20卷 / 04期

基金：

美国国家卫生研究院;

关键词：

5xFAD; Alzheimer's disease; amyloid; astrocytes; collaborative cross mice; genetic diversity; microglia; neurofilament light chain; resilience; GENOME-WIDE ASSOCIATION; NEUROFILAMENT LIGHT; AMYLOID DEPOSITION; RISK LOCI; BETA; MICROGLIA; NEURODEGENERATION; METAANALYSIS; PHENOTYPES; MUTATIONS;

D O I：

10.1002/alz.13753

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 strainswith 5xFADC57BL/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.

引用

页码：2794 / 2816

页数：23

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