ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Apathy Associated with Alzheimer's Disease.Current Alzheimer research · 2024Pooled it
- A collaborative framework for uncovering molecular and cellular drivers of VCID: Foundations for future interventions in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- The past, the present, and the future of preclinical mouse models for Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- WSB.APP/PS1 mice develop age-dependent cerebral amyloid angiopathy, cerebrovascular dysfunction, and white matter deficits.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Understanding the contribution of toxicant exposures to Alzheimer's disease and related dementias.Current opinion in neurobiology · 2026Review
- Neurovascular-metabolic dysregulation, metabolic connectomics, and metabolic functional changes in Alzheimer's disease: A preclinical and clinical comparison.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- PSEN1 mutant marmoset fibroblasts mimic multi-omic signatures of Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Multiscale metabolic covariance networks uncover stage-specific biomarker signatures across the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Magnetic resonance microscopy maps widespread effects of Alzheimer's disease on brain structures and behavior in mice.Nature neuroscience · 2026Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: implications for translational validity to the human.Frontiers in neuroscience · 2026Article
- TREM2-driven peripheral macrophage regulation in inflammatory diseases: implications extending beyond neurological disorders.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Recent advances in model systems for interrogating diseases of brain aging and associated dementia: Toward human-relevant endophenotypes.Current opinion in neurobiology · 2025Review
- Neurometabolic and vascular dysfunction as an early diagnostic for Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: Implications for translational validity to the human.bioRxiv : the preprint server for biology · 2025Article
- WSB.bioRxiv : the preprint server for biology · 2025Article
- Mesenchymal stem cell-derived exosomes: Shaping the next era of Alzheimer's disease treatment.World journal of stem cells · 2025Review
- Review
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
- Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model.Biomedicines · 2024Article
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25 authors.
Funding
Abstract
introductionMODEL-AD (Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late-onset Alzheimer's disease (LOAD) more accurately.
methodsWe created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid-beta (Aβ). Mice were subjected to a control diet or a high-fat/high-sugar diet (LOAD2+HFD). We assessed disease-relevant outcome measures in plasma and brain including neuroinflammation, Aβ, neurodegeneration, neuroimaging, and multi-omics.
resultsBy 18 months, LOAD2+HFD mice exhibited sex-specific neuron loss, elevated insoluble brain Aβ42, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function. Imaging showed reductions in brain volume and neurovascular uncoupling. Deficits in acquiring touchscreen-based cognitive tasks were observed. DISCUSSION: The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of LOAD prior to or independent of amyloid plaques and tau tangles. HIGHLIGHTS: By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL). Transcriptomics and proteomics showed changes in gene/proteins relating to a variety of disease-relevant processes including lipid metabolism and synaptic function. In vivo imaging revealed an age-dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT). LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen-based cognitive tasks.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.