Objectives: In the present study, we have tested whether MRI T relaxation time is a sensitive marker to detect early stages of amyloidosis and gliosis in the young 5xFAD transgenic mouse, a well-established animal model for Alzheimer's disease.
Materials And Methods: 5xFAD and wild-type mice were imaged in a 4.7 T Varian horizontal bore MRI system to generate T quantitative maps using the spin-echo multi-slice sequence. Following immunostaining for glial fibrillary acidic protein, Iba-1, and amyloid-β, T and area fraction of staining were quantified in the posterior parietal and primary somatosensory cortex and corpus callosum.
Results: In comparison with age-matched wild-type mice, we observed first signs of amyloidosis in 2.5-month-old 5xFAD mice, and development of gliosis in 5-month-old 5xFAD mice. In contrast, MRI T relaxation times of young, i.e., 2.5- and 5-month-old, 5xFAD mice were not significantly different to those of age-matched wild-type controls. Furthermore, although disease progression was detectable by increased amyloid-β load in the brain of 5-month-old 5xFAD mice compared with 2.5-month-old 5xFAD mice, MRI T relaxation time did not change.
Conclusions: In summary, our data suggest that MRI T relaxation time is neither a sensitive measure of disease onset nor progression at early stages in the 5xFAD mouse transgenic mouse model.
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http://dx.doi.org/10.1007/s10334-016-0593-9 | DOI Listing |
Nat Aging
January 2025
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea.
The abnormal deposition of amyloid β (Aβ), produced by proteolytic cleavage events of amyloid precursor protein involving the protease γ-secretase and subsequent polymerization into amyloid plaques, plays a key role in the neuropathology of Alzheimer's disease (AD). Here we show that ErbB3 binding protein 1 (EBP1)/proliferation-associated 2G4 (PA2G4) interacts with presenilin, a catalytic subunit of γ-secretase, inhibiting Aβ production. Mice lacking forebrain Ebp1/Pa2g4 recapitulate the representative phenotypes of late-onset sporadic AD, displaying an age-dependent increase in Aβ deposition, amyloid plaques and cognitive dysfunction.
View Article and Find Full Text PDFPhytomedicine
December 2024
Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center at the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address:
Background: Ginkgo biloba leaf extract EGb 761® has shown clinical efficacy in patients with mild cognitive impairment and dementia. However, the pharmacological action of EGb 761® in Alzheimer's disease (AD) remains unclear and molecular mechanisms targeted in the brain are not completely understood.
Hypothesis/purpose: We aimed to investigate 1) the potential sex-dependent effects of oral administration of EGb 761® in 5xFAD mice, an AD mouse model, and 2) the underlying microglial subtype responsible for the observed anti-inflammatory effects in the brain.
Alzheimers Dement
January 2025
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Introduction: Plaques are a hallmark feature of Alzheimer's disease (AD). We found that the loss of mucosal-associated invariant T (MAIT) cells and their antigen-presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting dystrophic neurites.
View Article and Find Full Text PDFBiomolecules
December 2024
Inst Neurophysiopathol, CNRS, INP, Aix-Marseille Univ, 13005 Marseille, France.
We previously reported that membrane-type 5-matrix metalloproteinase (MT5-MMP) deficiency not only reduces pathological hallmarks of Alzheimer's disease (AD) in 5xFAD (Tg) mice in vivo but also impairs interleukin-1 beta (IL-1β)-mediated neuroinflammation and Aβ production in primary Tg immature neural cell cultures after 11 days in vitro. We now investigate the effect of MT5-MMP on incipient pathogenic pathways that are activated in cortical primary cultures at 21-24 days in vitro (DIV), during which time neurons are organized into a functional mature network. Using wild-type (WT), MT5-MMP (MT5), 5xFAD (Tg), and 5xFADxMT5-MMP (TgMT5) mice, we generated primary neuronal cultures that were exposed to IL-1β and/or different proteolytic system inhibitors.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Pharmacy, the Second Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, China.
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and the aggregation of tau protein, resulting in intense memory loss and dementia. Diabetes-associated cognitive dysfunction (DACD) is a complication of diabetes mellitus, which is associated with decreased cognitive function and impaired memory. A growing body of literature emphasize the involvement of microglia in AD and DACD.
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