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TitleCryo-EM structures of cotton wool plaques' amyloid β and of tau filaments in dominantly inherited Alzheimer disease.
Journal, issue, pagesActa Neuropathol, Vol. 148, Issue 1, Page 20, Year 2024
Publish dateAug 15, 2024
AuthorsMd Rejaul Hoq / Anllely Fernandez / Frank S Vago / Grace I Hallinan / Sakshibeedu R Bharath / Daoyi Li / Kadir A Ozcan / Holly J Garringer / Wen Jiang / Ruben Vidal / Bernardino Ghetti /
PubMed AbstractCotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the ...Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the presenilin 1 (PSEN1) gene. CWPs are round, eosinophilic amyloid-β (Aβ) plaques that lack an amyloid core and are recognizable, but not fluorescent, in Thioflavin S (ThS) preparations. Amino-terminally truncated and post-translationally modified Aβ peptide species are the main component of CWPs. Tau immunopositive neurites may be present in CWPs. In addition, neurofibrillary tangles coexist with CWPs. Herein, we report the structure of Aβ and tau filaments isolated from brain tissue of individuals affected by DIAD caused by the PSEN1 V261I and A431E mutations, with the CWP neuropathologic phenotype. CWPs are predominantly composed of type I Aβ filaments present in two novel arrangements, type Ic and type Id; additionally, CWPs contain type I and type Ib Aβ filaments. Tau filaments have the AD fold, which has been previously reported in sporadic AD and DIAD. The formation of type Ic and type Id Aβ filaments may be the basis for the phenotype of CWPs. Our data are relevant for the development of PET imaging methodologies to best detect CWPs in DIAD.
External linksActa Neuropathol / PubMed:39147931 / PubMed Central
MethodsEM (helical sym.)
Resolution2.6 - 3.3 Å
Structure data

46417

9czi

EMDB-46417, PDB-9czi:
Paired helical tau filaments in dominantly inherited Alzheimer disease with cotton wool plaques
Method: EM (helical sym.) / Resolution: 3.0 Å

46420

9czl

EMDB-46420, PDB-9czl:
Straight tau filaments in dominantly inherited Alzheimer disease with cotton wool plaques
Method: EM (helical sym.) / Resolution: 2.9 Å

46422

9czn

EMDB-46422, PDB-9czn:
Type Ic amyloid-beta 42 filaments in dominantly inherited Alzheimer disease with cotton wool plaques
Method: EM (helical sym.) / Resolution: 2.6 Å

46424

9czp

EMDB-46424, PDB-9czp:
Type Id amyloid-beta 42 filaments in dominantly inherited Alzheimer disease with cotton wool plaques
Method: EM (helical sym.) / Resolution: 3.3 Å

Source
  • homo sapiens (human)
KeywordsNEUROPEPTIDE / Tau filaments / PHF / cotton wool plaques / neurodegeneration / PROTEIN FIBRIL / SF / Amyloid filaments

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