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Structure paper

TitleCryo-EM of Aβ fibrils from mouse models find tg-APP fibrils resemble those found in patients with sporadic Alzheimer's disease.
Journal, issue, pagesNat Neurosci, Vol. 26, Issue 12, Page 2073-2080, Year 2023
Publish dateNov 16, 2023
AuthorsMara Zielinski / Fernanda S Peralta Reyes / Lothar Gremer / Sarah Schemmert / Benedikt Frieg / Luisa U Schäfer / Antje Willuweit / Lili Donner / Margitta Elvers / Lars N G Nilsson / Stina Syvänen / Dag Sehlin / Martin Ingelsson / Dieter Willbold / Gunnar F Schröder /
PubMed AbstractThe use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties ...The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer's disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APP and APP23 models. The tg-APP mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer's disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer's disease.
External linksNat Neurosci / PubMed:37973869 / PubMed Central
MethodsEM (helical sym.)
Resolution3.0 - 4.2 Å
Structure data

16942

8ol2

EMDB-16942, PDB-8ol2:
Murine type II Abeta fibril from APP23 mouse
Method: EM (helical sym.) / Resolution: 3.0 Å

16944

8ol3

EMDB-16944, PDB-8ol3:
Murine type III Abeta fibril from APP/PS1 mouse
Method: EM (helical sym.) / Resolution: 3.5 Å

16949

8ol5

EMDB-16949, PDB-8ol5:
Murine type II Abeta fibril from ARTE10 mouse
Method: EM (helical sym.) / Resolution: 3.4 Å

16952

8ol6

EMDB-16952, PDB-8ol6:
Murine type II Abeta fibril from tgAPPSwe mouse
Method: EM (helical sym.) / Resolution: 3.8 Å

16953

8ol7

EMDB-16953, PDB-8ol7:
MurineArc type I Abeta fibril from tg-APPArcSwe mouse
Method: EM (helical sym.) / Resolution: 3.0 Å

16957

8olg

EMDB-16957, PDB-8olg:
DI2 Abeta fibril from tg-SwDI mouse
Method: EM (helical sym.) / Resolution: 4.2 Å

16959

8oln

EMDB-16959, PDB-8oln:
DI1 Abeta fibril from tg-SwDI mouse
Method: EM (helical sym.) / Resolution: 3.3 Å

16960

8olo

EMDB-16960, PDB-8olo:
Murine type III Abeta fibril from ARTE10 mouse
Method: EM (helical sym.) / Resolution: 3.5 Å

16961

8olq

EMDB-16961, PDB-8olq:
DI3 Abeta fibril from tg-SwDI mouse
Method: EM (helical sym.) / Resolution: 4.0 Å

Source
  • Mus musculus (house mouse)
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Amyloid fibril

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