9CZP

Type Id amyloid-beta 42 filaments in dominantly inherited Alzheimer disease with cotton wool plaques

Summary for 9CZP

• Entry DOI: 10.2210/pdb9czp/pdb
• EMDB information: 46424
• Descriptor: Amyloid-beta protein 42 (1 entity in total)
• Functional Keywords: amyloid filaments, cotton wool plaques, neurodegeneration, neuropeptide, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 20
• Total formula weight: 71202.56

Authors

Hoq, M.R.,Vago, F.S.,Ozcan, K.A.,Bharath, S.R. (deposition date: 2024-08-05, release date: 2024-10-02)

Primary citation

Hoq, M.R.,Fernandez, A.,Vago, F.S.,Hallinan, G.I.,Bharath, S.R.,Li, D.,Ozcan, K.A.,Garringer, H.J.,Jiang, W.,Vidal, R.,Ghetti, B.
Cryo-EM structures of cotton wool plaques' amyloid beta and of tau filaments in dominantly inherited Alzheimer disease.
Acta Neuropathol, 148:20-20, 2024

PubMed Abstract: 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.

PubMed: 39147931
DOI: 10.1007/s00401-024-02786-y

Experimental method

ELECTRON MICROSCOPY (3.3 Å)