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Cited by 22Alzheimer's disease research and treatmentsDown syndrome and intellectual disability researchDementia and Cognitive Impairment Research

Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches

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Farrell, Clíona, Mumford, Paige, Wiseman, Frances K.·2022·Frontiers in Neuroscience
DOI 10.3389/fnins.2022.909669PMC PMC9209729
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Abstract

There are an estimated 6 million people with Down syndrome (DS) worldwide. In developed countries, the vast majority of these individuals will develop Alzheimer's disease neuropathology characterized by the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles within the brain, which leads to the early onset of dementia (AD-DS) and reduced life-expectancy. The mean age of onset of clinical dementia is ~55 years and by the age of 80, approaching 100% of individuals with DS will have a dementia diagnosis. DS is caused by trisomy of chromosome 21 (Hsa21) thus an additional copy of a gene(s) on the chromosome must cause the development of AD neuropathology and dementia. Indeed, triplication of the gene APP which encodes the amyloid precursor protein is sufficient and necessary for early onset AD (EOAD), both in people who have and do not have DS. However, triplication of other genes on Hsa21 leads to profound differences in neurodevelopment resulting in intellectual disability, elevated incidence of epilepsy and perturbations to the immune system. This different biology may impact on how AD neuropathology and dementia develops in people who have DS. Indeed, genes on Hsa21 other than APP when in three-copies can modulate AD-pathogenesis in mouse preclinical models. Understanding this biology better is critical to inform drug selection for AD prevention and therapy trials for people who have DS. Here we will review rodent preclinical models of AD-DS and how these can be used for both in vivo and ex vivo (cultured cells and organotypic slice cultures) studies to understand the mechanisms that contribute to the early development of AD in people who have DS and test the utility of treatments to prevent or delay the development of disease.

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Cited by

Sorted by citations

Authors
Farrell, C., Mumford, P., & Wiseman, F. K.
Affiliations
UK Dementia Research Institute (GB)
Corresponding author
Wiseman, Frances K.
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2022-06-07
Volume
16
Pages
909669-909669
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2022.909669
PMC
PMC9209729
OpenAlex
W4281905920
Cited by
22
References
37
Citations by year
2026: 4 · 2025: 8 · 2024: 6 · 2023: 2 · 2022: 2
FWCI
0.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Alzheimer’s Research UK
  • UK Dementia Research Institute
  • Alzheimer's Society
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Down syndrome, Alzheimer's disease, amyloid plaques, neurofibrillary tangles, early-onset Alzheimer's disease, rodent models, organotypic slice cultures, cultured cells, disease prevention, drug testing, intellectual disability, epilepsy

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