Dataset Information

Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice.

ABSTRACT: The amyloid plaque is a hallmark of Alzheimer's disease. The accumulation of the amyloid precursor protein (APP) in the neuronal structure is assumed to lead to amyloid plaque formation through the excessive production of β-amyloid protein. To study the relationship between the neuronal accumulation of APP and amyloid plaque formation, we histologically analyzed their development in the different brain regions in 3xTg-AD mice, which express Swedish mutated APP (APP_SWE) in the neurons. Observation throughout the brain revealed APP_SWE-positive somata in the broad regions. Quantitative model analysis showed that the somatic accumulation of APP_SWE developed firstly in the hippocampus from a very early age (<1 month) and proceeded slower in the isocortex. In line with this, the hippocampus was the first region to form amyloid plaques at the age of 9-12 months, while amyloid plaques were rarely observed in the isocortex. Females had more APP_SWE-positive somata and plaques than males. Furthermore, amyloid plaques were observed in the lateral septum and pontine grey, which did not contain APP_SWE-positive somata but only the APP_SWE-positive fibers. These results suggested that neuronal accumulation of APP_SWE, both in somatodendritic and axonal domains, is closely related to the formation of amyloid plaques.

SUBMITTER: Ono M

PROVIDER: S-EPMC11002285 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice.

Ono Munenori M Ito Tetsufumi T Yamaki Sachiko S Hori Yoshie Y Zhou Qing Q Zhao Xirun X Muramoto Shinji S Yamamoto Ryo R Furuyama Takafumi T Sakata-Haga Hiromi H Hatta Toshihisa T Hamaguchi Tsuyoshi T Kato Nobuo N

Heliyon 20240330 7

The amyloid plaque is a hallmark of Alzheimer's disease. The accumulation of the amyloid precursor protein (APP) in the neuronal structure is assumed to lead to amyloid plaque formation through the excessive production of β-amyloid protein. To study the relationship between the neuronal accumulation of APP and amyloid plaque formation, we histologically analyzed their development in the different brain regions in 3xTg-AD mice, which express Swedish mutated APP (APP<sub>SWE</sub>) in the neurons. ...[more]

PMID: 38596059

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Project description:The widely studied triple transgenic (3xTg-AD) mouse provides a robust model of Alzheimer's disease (AD) with region dependent patterns of progressive amyloid-β (Aß) and tau pathology. Using diffusion MRI (dMRI), we investigated the sensitivity of dMRI measures in capturing AD pathology associated microstructure alterations in older 3xTg-AD mice, and the degree to which dMRI changes correlate with measurements of Aβ and tau pathology. 3xTg-AD and normal control (NC) mice, 15 to 21 months of age, were used in this study. In vivo dMRI data were acquired for the generation of diffusion tensor (DT) and diffusional kurtosis (DK) measures within the hippocampus and fimbria (Fi). For these same brain regions, Aβ and tau pathology were quantified by morphological analysis of Aß1-42 and AT8 immunoreactivity. Two-tailed, two-sample t-tests were performed to assess group differences in each brain region of interest (ROI), with the Benjamini-Hochberg false discovery rate (FDR) method being applied to adjust for multiple comparisons. Spearman correlation coefficients were calculated to investigate associations between diffusion and morphological measures. Our results revealed, depending on the brain region, DT and DK measures were able to detect group differences. In the dorsal hippocampus (HD), fractional anisotropy (FA) was significantly higher in the 3xTg-AD mice compared with NC mice. In the subiculum (SUB), FA, axial diffusivity (D||) and radial kurtosis (K┴) were significantly higher in 3xTg-AD mice compared with NC mice. Morphological quantification of Aß1-42 and AT8 immunoreactivity showed elevated Aß and tau in the Fi, ventral hippocampus (HV) and SUB of 3xTg-AD mice. The presence of Aβ and tau was significantly correlated with several DT and DK measures, particularly in the SUB, where an increase in tau correlated with an increase in mean kurtosis (MK) and K┴. This work demonstrates significant dMRI differences between older 3xTg-AD and NC mice in the hippocampus and Fi. Significant correlations were found between dMRI and morphological measures of Aβ and tau pathology. These results support the potential of dMRI-derived parameters as biomarkers of AD pathology. Since the imaging methods employed here are easily translatable to clinical MRI, our results are also relevant for human AD patients.

Dataset Information

Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice.

Publications

Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice.

Similar Datasets

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