Detail of Fig3b_inclusion_DLB_5



Project
Title
Z-stack images of DLB/PDD seed transduction cells
Description
Z-stack images of dementia with Lewy bodies (DLB)/PD with dementia (PDD) seed transducted HEK293 cell line stably expressing green fluorescent protein (GFP)-fused human alpha-synuclein with A53T mutation (293-SynG). The fixed cells were observed by super-resolution structured illumination microscopy (SR-SIM).
Release, Updated
2025-01-31
License
CC BY
Kind
Image data
File Formats
.tif
Data size
17.6 MB

Organism
Homo sapiens ( NCBI:txid9606 )
Strain(s)
-
Cell Line
HEK293 ( CLO_0001230 )

Datatype
-
Molecular Function (MF)
Biological Process (BP)
inclusion body assembly ( GO:0070841 )
Cellular Component (CC)
inclusion body ( GO:0016234 )
Biological Imaging Method
fluorescence microscopy ( Fbbi:00000246 )
structured illumination microscopy ( Fbbi:00000332 )
X scale
264.58 micrometer
Y scale
264.58 micrometer
Z scale
3 micrometer
T scale
-

Image Acquisition
Experiment type
-
Microscope type
-
Acquisition mode
-
Contrast method
-
Microscope model
-
Detector model
-
Objective model
-
Filter set
-

Summary of Methods
Okuzumi A, Hatano T, Matsumoto G, Nojiri S, Ueno SI, Imamichi-Tatano Y, Kimura H, Kakuta S, Kondo A, Fukuhara T, Li Y, Funayama M, Saiki S, Taniguchi D, Tsunemi T, McIntyre D, Gerardy JJ, Mittelbronn M, Kruger R, Uchiyama Y, Nukina N, Hattori N. Propagative alpha-synuclein seeds as serum biomarkers for synucleinopathies. Nat Med. 2023 Jun;29(6):1448-1455.
Related paper(s)

Ayami Okuzumi, Taku Hatano, Gen Matsumoto, Shuko Nojiri, Shin-Ichi Ueno, Yoko Imamichi-Tatano, Haruka Kimura, Soichiro Kakuta, Akihide Kondo, Takeshi Fukuhara, Yuanzhe Li, Manabu Funayama, Shinji Saiki, Daisuke Taniguchi, Taiji Tsunemi, Deborah McIntyre, Jean-Jacques Gerardy, Michel Mittelbronn, Rejko Kruger, Yasuo Uchiyama, Nobuyuki Nukina, Nobutaka Hattori (2023) Propagative alpha-synuclein seeds as serum biomarkers for synucleinopathies., Nature medicine

Published in 2023 May 29 (Electronic publication in May 29, 2023, midnight )

(Abstract) Abnormal alpha-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic beta-sheet seed conformation of alpha-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic alpha-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95-0.99)/AUC: 0.93 (95% CI 0.84-1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49-0.79)/AUC: 0.73 (95% CI 0.49-0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74-0.99)) and MSA (AUC: 0.80 (95% CI 0.65-0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples.

Contact
Nobutaka Hattori , Juntendo University , Department of Neurology , Department of Neurology
Contributors
Ayami Okuzumi, Soichiro Kakuta, Yasuo Uchiyama

OMERO Dataset
OMERO Project
Source