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TitleCryo-EM structures of amyloid-β and tau filaments in Down syndrome.
Journal, issue, pagesNat Struct Mol Biol, Vol. 31, Issue 6, Page 903-909, Year 2024
Publish dateMar 29, 2024
AuthorsAnllely Fernandez / Md Rejaul Hoq / Grace I Hallinan / Daoyi Li / Sakshibeedu R Bharath / Frank S Vago / Xiaoqi Zhang / Kadir A Ozcan / Kathy L Newell / Holly J Garringer / Wen Jiang / Bernardino Ghetti / Ruben Vidal /
PubMed AbstractAdult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is ...Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is unknown. Here we report the structure of Aβ and tau filaments from two DS brains. We found two Aβ filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aβ filaments (I and II) identical to those found in sporadic and familial AD. Tau filaments (paired helical filaments and straight filaments) were identical to those in AD, supporting the notion of a common mechanism through which amyloids trigger aggregation of tau. This knowledge is important for understanding AD in DS and assessing whether adults with DS could be included in AD clinical trials.
External linksNat Struct Mol Biol / PubMed:38553642 / PubMed Central
MethodsEM (helical sym.)
Resolution2.9 - 3.8 Å
Structure data

40411

8seh

EMDB-40411, PDB-8seh:
PHF Tau from Down Syndrome
Method: EM (helical sym.) / Resolution: 2.9 Å

40413

8sei

EMDB-40413, PDB-8sei:
SF Tau from Down Syndrome
Method: EM (helical sym.) / Resolution: 2.9 Å

40416

8sej

EMDB-40416, PDB-8sej:
Type I beta-amyloid 42 Filaments from Down syndrome
Method: EM (helical sym.) / Resolution: 3.17 Å

40419

8sek

EMDB-40419, PDB-8sek:
Type IIIa beta-amyloid 40 Filaments from Down syndrome
Method: EM (helical sym.) / Resolution: 3.5 Å

40421

8sel

EMDB-40421, PDB-8sel:
Type IIIb beta-amyloid 40 Filaments from Down Syndrome
Method: EM (helical sym.) / Resolution: 3.8 Å

Source
  • homo sapiens (human)
  • homo (humans)
KeywordsNEUROPEPTIDE / PHF Tau / Tau Filament / Down Syndrome / Human Trisomy 21 / SF Tau / Beta Amyloid filaments

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