ArticleFluids and barriers of the CNS2024
Cognitive decline, Aβ pathology, and blood-brain barrier function in aged 5xFAD mice.
Article in Fluids and barriers of the CNS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- Multispectral photoacoustic microscopy and NIR-II fluorescence imaging of TREM2-positive microglia in Aβ-driven Alzheimer's pathogenesis.Fundamental research · 2026Article
- Nobiletin Ameliorates Alzheimer's Disease Pathology by Reducing Oxidative Stress and Neuroinflammation Through the AMPK/SIRT1/PGC-1Biomedicines · 2026Article
- Single-cell RNA sequencing reveals disease associated changes in brain endothelial cells in the 5XFAD mouse.Fluids and barriers of the CNS · 2026Article
- Frequency-Specific Transcranial Photobiomodulation Elicits Complementary Glial Mechanisms for Neurovascular Protection and Amyloid Clearance in Alzheimer Disease.Cyborg and bionic systems (Washington, D.C.) · 2026Article
- Meningeal vascular Aβ deposition associates with cerebral hypoperfusion and compensatory collateral remodeling.Alzheimer's research & therapy · 2025Article
- Crocin Ameliorates Cognitive Impairment and Pathological Changes in Alzheimer's Disease Model Mice by Regulating Gut Microbiota.Food science & nutrition · 2025Article
- A novel miR-4536-3p inhibition ameliorates Alzheimer's disease by reducing Aβ accumulation and tau phosphorylation.Alzheimer's research & therapy · 2025Article
- A Positive Allosteric Modulator of the SERCA Pump Rescues Hippocampal Neuronal Circuits Dysfunction and Cognitive Defects in a Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.Fluids and barriers of the CNS · 2025Article
- Chemogenetic Modulation of Astrocytic Activity Rescues Hippocampus Associated Neurodegeneration in Alzheimer's Disease Mice Model 5xFAD.Neural plasticity · 2025Article
- Platycodin D and voluntary running synergistically ameliorate memory deficits in 5 × FAD mice via mediating neuromodulation and neuroinflammation.Frontiers in aging neuroscience · 2024Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundPatients with Alzheimer's disease (AD) develop blood-brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood-brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.
methods5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the brain by two-photon microscopy. Images were processed and segmented to obtain intravascular intensity, extravascular intensity, and vessel diameters as a measure of barrier integrity. Mice were sacrificed after in vivo imaging to isolate brain and plasma for measuring Aβ levels. The effect of age and genotype were evaluated for each assay using generalized or cumulative-linked logistic mixed-level modeling and model selection by Akaike Information Criterion (AICc). Pairwise comparisons were used to identify outcome differences between the two groups.
results5xFAD mice displayed spatial memory deficits compared to age-matched WT mice in the MWM assay, which worsened with age. Memory impairment was evident in 5xFAD mice by 2-threefold higher escape latencies, twofold greater cumulative distances until they reach the platform, and twice as frequent use of repetitive search strategies in the pool when compared with age-matched WT mice. Presence of the rd1 allele worsened MWM performance in 5xFAD mice at all ages but did not alter the rate of learning or probe trial outcomes. 9.5-month-old 15.5-month-old 5xFAD mice had twofold higher brain Aβ
conclusion5xFAD mice continue to develop spatial memory deficits and increased Aβ brain levels while aging. Given in vivo MP imaging limitations, further investigation with smaller molecular weight markers combined with advanced imaging techniques would be needed to reliably assess subtle differences in barrier integrity in aged mice.
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