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- EMDB-18301: In-tissue cryo electron tomograms of App^NL-G-F amyloid plaques -

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Basic information

Entry
Database: EMDB / ID: EMD-18301
TitleIn-tissue cryo electron tomograms of App^NL-G-F amyloid plaques
Map dataReconstructed tomogram DS3-TS1
Sample
  • Tissue: High-pressure frozen App^NL-G-F brain tissue containing Arctic amyloid-beta plaques
KeywordsAmyloid / amyloid beta / alzheimers / neurodegeneration / plaque / tomography / in situ / brain / cryoCLEM / pathology / PROTEIN FIBRIL
Biological speciesMus musculus (house mouse)
Methodelectron tomography / cryo EM
AuthorsLeistner C / Wilkinson M / Burgess A / Lovatt M / Goodbody S / Xu Y / Deuchars S / Radford SE / Ranson NA / Frank RAW
Funding support United Kingdom, 5 items
OrganizationGrant numberCountry
Royal SocietyRSRP/R1/211057 United Kingdom
Medical Research Council (MRC, United Kingdom)MR/T011149/1 United Kingdom
Wellcome Trust221524/Z/20/Z United Kingdom
Wellcome Trust208395/Z/17/Z United Kingdom
UK Research and Innovation (UKRI)MR/V022644/1 United Kingdom
CitationJournal: Nat Commun / Year: 2023
Title: The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain.
Authors: Conny Leistner / Martin Wilkinson / Ailidh Burgess / Megan Lovatt / Stanley Goodbody / Yong Xu / Susan Deuchars / Sheena E Radford / Neil A Ranson / René A W Frank /
Abstract: Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. ...Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the in situ molecular architecture of Aβ fibrils in the App familial AD mouse model containing the Arctic mutation and an atomic model of ex vivo purified Arctic Aβ fibrils. We show that in-tissue Aβ fibrils are arranged in a lattice or parallel bundles, and are interdigitated by subcellular compartments, extracellular vesicles, extracellular droplets and extracellular multilamellar bodies. The Arctic Aβ fibril differs significantly from an earlier App fibril structure, indicating a striking effect of the Arctic mutation. These structural data also revealed an ensemble of additional fibrillar species, including thin protofilament-like rods and branched fibrils. Together, these results provide a structural model for the dense network architecture that characterises β-amyloid plaque pathology.
History
DepositionAug 23, 2023-
Header (metadata) releaseSep 20, 2023-
Map releaseSep 20, 2023-
UpdateSep 20, 2023-
Current statusSep 20, 2023Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_18301.png

Downloads & links

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Map

FileDownload / File: emd_18301.map.gz / Format: CCP4 / Size: 252.3 MB / Type: IMAGE STORED AS SIGNED BYTE
AnnotationReconstructed tomogram DS3-TS1
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
13.7 Å/pix.
x 297 pix.
= 4068.9 Å		13.7 Å/pix.
x 928 pix.
= 12713.6 Å		13.7 Å/pix.
x 960 pix.
= 13152. Å

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

generated in cubic-lattice coordinate

Voxel sizeX=Y=Z: 13.7 Å
Density

Histogram

Histogram (log scale)
Minimum - Maximum-128.0 - 127.0
Average (Standard dev.)-20.138327 (±9.753087000000001)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-1616149
Dimensions928960297
Spacing960928297
CellA: 13152.0 Å / B: 12713.6 Å / C: 4068.9 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Reconstructed tomogram DS3-TS4

Fileemd_18301_additional_1.map
AnnotationReconstructed tomogram DS3-TS4
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : High-pressure frozen App^NL-G-F brain tissue containing Arctic am...

EntireName: High-pressure frozen App^NL-G-F brain tissue containing Arctic amyloid-beta plaques
Components
  • Tissue: High-pressure frozen App^NL-G-F brain tissue containing Arctic amyloid-beta plaques

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Supramolecule #1: High-pressure frozen App^NL-G-F brain tissue containing Arctic am...

SupramoleculeName: High-pressure frozen App^NL-G-F brain tissue containing Arctic amyloid-beta plaques
type: tissue / ID: 1 / Parent: 0
Source (natural)Organism: Mus musculus (house mouse) / Strain: App^NL-G-F / Organ: Brain

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Experimental details

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Structure determination

Methodcryo EM
Processingelectron tomography
Aggregation statetissue

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Sample preparation

BufferpH: 7.4
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec.
VitrificationCryogen name: ETHANE
High pressure freezingInstrument: OTHER
Details: 2000 bar. The value given for _em_high_pressure_freezing.instrument is Leica EM ICE. This is not in a list of allowed values {'OTHER', 'EMS-002 RAPID IMMERSION FREEZER', 'LEICA EM PACT2', ...Details: 2000 bar. The value given for _em_high_pressure_freezing.instrument is Leica EM ICE. This is not in a list of allowed values {'OTHER', 'EMS-002 RAPID IMMERSION FREEZER', 'LEICA EM PACT2', 'LEICA EM HPM100', 'LEICA EM PACT', 'BAL-TEC HPM 010'} so OTHER is written into the XML file.
Cryo protectant20% Dextran 40000
SectioningUltramicrotomy - Instrument: cryo-ultramicrotome (Leica EM FC7)
Ultramicrotomy - Temperature: 123 K / Ultramicrotomy - Final thickness: 100

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 2.0 sec. / Average electron dose: 61.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 4.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionSoftware - Name: IMOD / Number images used: 61

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