Dataset Information

Label-free multiphoton imaging of ?-amyloid plaques in Alzheimer's disease mouse models.

ABSTRACT: ? -Amyloid ( A ? ) plaque, representing the progressive accumulation of the protein that mainly consists of A ? , is one of the prominent pathological hallmarks of Alzheimer's disease (AD). Label-free imaging of A ? plaques holds the potential to be a histological examination tool for diagnosing AD. We applied label-free multiphoton microscopy to identify extracellular A ? plaque as well as intracellular A ? accumulation for the first time from AD mouse models. We showed that a two-photon-excited fluorescence signal is a sensitive optical marker for revealing the spatial-temporal progression and the surrounding morphological changes of A ? deposition, which demonstrated that both extracellular and intracellular A ? accumulations play an important role in the progression of AD. Moreover, combined with a custom-developed image-processing program, we established a rapid method to visualize different degrees of A ? deposition by color coding. These results provide an approach for investigating pathophysiology of AD that can complement traditional biomedical procedures.

SUBMITTER: Wang S

PROVIDER: S-EPMC6850002 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Label-free multiphoton imaging of <i>β</i>-amyloid plaques in Alzheimer's disease mouse models.

Wang Shu S Lin Bingbing B Lin Guimin G Sun Caihong C Lin Ruolan R Huang Jia J Tao Jing J Wang Xingfu X Wu Yunkun Y Chen Lidian L Chen Jianxin J

Neurophotonics 20191001 4

β -Amyloid ( A β ) plaque, representing the progressive accumulation of the protein that mainly consists of A β , is one of the prominent pathological hallmarks of Alzheimer's disease (AD). Label-free imaging of A β plaques holds the potential to be a histological examination tool for diagnosing AD. We applied label-free multiphoton microscopy to identify extracellular A β plaque as well as intracellular A β accumulation for the first time from AD mouse models. We showed that a two-photon- ...[more]

PMID: 31737743

Similar Datasets

Project description:Beta-amyloid (Aβ) plaque pathology is one of the most prominent histopathological feature of Alzheimer's disease (AD). The exact pathogenic mechanisms linking Aβ to AD pathogenesis remain however not fully understood. Recent advances in amyloid-targeting pharmacotherapies highlight the critical relevance of Aβ aggregation for understanding the molecular basis of AD pathogenesis. We developed a novel, integrated, tetramodal chemical imaging paradigm for acquisition of trimodal mass spectrometry imaging (MSI) and interlaced fluorescent microscopy from a single tissue section. We used this approach to comprehensively investigate lipid-Aβ correlates at single plaques in two different mouse models of AD (tgAPPSwe and tgAPPArcSwe) with varying degrees of intrinsic properties affecting amyloid aggregation. Integration of the multimodal imaging data and multivariate data analysis identified characteristic patterns of plaque-associated lipid- and peptide localizations across both mouse models. Correlative fluorescence microscopy using structure-sensitive amyloid probes identified intra-plaque structure-specific lipid- and Aβ patterns, including Aβ 1-40 and Aβ 1-42 along with gangliosides (GM), phosphoinositols (PI), conjugated ceramides (CerP and PE-Cer), and lysophospholipids (LPC, LPA, and LPI). Single plaque correlation analysis across all modalities further revealed how these distinct lipid species were associated with Aβ peptide deposition across plaque heterogeneity, indicating different roles for those lipids in plaque growth and amyloid fibrillation, respectively. Here, conjugated ceramide species correlated with Aβ core formation indicating their involvement in initial plaque seeding or amyloid maturation. In contrast, LPI and PI were solely correlated with general plaque growth. In addition, GM1 and LPC correlated with continuous Aβ deposition and maturation. The results highlight the potential of this comprehensive multimodal imaging approach and implement distinct lipids in amyloidogenic proteinopathy.

Dataset Information

Label-free multiphoton imaging of ?-amyloid plaques in Alzheimer's disease mouse models.

Publications

Label-free multiphoton imaging of <i>β</i>-amyloid plaques in Alzheimer's disease mouse models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets