Cryo-EM structures of amyloid-β and tau filaments in Down syndrome

Fernandez, Anllely; Hoq, Md Rejaul; Hallinan, Grace I.; Li, Daoyi; Bharath, Sakshibeedu R.; Vago, Frank S.; Zhang, Xiaoqi; Ozcan, Kadir A.; Newell, Kathy L.; Garringer, Holly J.; Jiang, Wen; Ghetti, Bernardino; Vidal, Ruben

doi:10.1038/s41594-024-01252-3

Cryo-EM structures of amyloid-β and tau filaments in Down syndrome

Documentdetail

ID kaart

doi:10.1038/s41594-024-01252-3...

Auteur

Fernandez, Anllely Hoq, Md Rejaul Hallinan, Grace I. Li, Daoyi Bharath, Sakshibeedu R. Vago, Frank S. Zhang, Xiaoqi Ozcan, Kadir A. Newell, Kathy L. Garringer, Holly J. Jiang, Wen Ghetti, Bernardino Vidal, Ruben

Langue

Editor

Nature

Categorie

Life Sciences

Jaar

2024

vermelding datum

03-04-2024

Trefwoorden

filaments amyloid-β disease alzheimer syndrome ad tau ds

Metriek

Beschrijving

Here, using cryo-EM, authors reveal that amyloid-β and tau are identical in Alzheimer disease and Down syndrome.

This has implications for assessing whether adults with Down syndrome could be included in Alzheimer disease clinical trials.

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_40 filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aβ_42 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.

Fernandez, Anllely,Hoq, Md Rejaul,Hallinan, Grace I.,Li, Daoyi,Bharath, Sakshibeedu R.,Vago, Frank S.,Zhang, Xiaoqi,Ozcan, Kadir A.,Newell, Kathy L.,Garringer, Holly J.,Jiang, Wen,Ghetti, Bernardino,Vidal, Ruben, 2024, Cryo-EM structures of amyloid-β and tau filaments in Down syndrome, Nature