In:
eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-10-15)
Abstract:
Alzheimer’s disease (AD) pathology is characterized by plaques of amyloid beta (Aβ) and neurofibrillary tangles of tau. Aβ aggregation is thought to occur at early stages of the disease, and ultimately gives way to the formation of tau tangles which track with cognitive decline in humans. Here, we report the crystal structure of an Aβ core segment determined by MicroED and in it, note characteristics of both fibrillar and oligomeric structure. Using this structure, we designed peptide-based inhibitors that reduce Aβ aggregation and toxicity of already-aggregated species. Unexpectedly, we also found that these inhibitors reduce the efficiency of Aβ-mediated tau aggregation, and moreover reduce aggregation and self-seeding of tau fibrils. The ability of these inhibitors to interfere with both Aβ and tau seeds suggests these fibrils share a common epitope, and supports the hypothesis that cross-seeding is one mechanism by which amyloid is linked to tau aggregation and could promote cognitive decline.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.46924.001
DOI:
10.7554/eLife.46924.002
DOI:
10.7554/eLife.46924.003
DOI:
10.7554/eLife.46924.004
DOI:
10.7554/eLife.46924.005
DOI:
10.7554/eLife.46924.006
DOI:
10.7554/eLife.46924.008
DOI:
10.7554/eLife.46924.007
DOI:
10.7554/eLife.46924.009
DOI:
10.7554/eLife.46924.012
DOI:
10.7554/eLife.46924.010
DOI:
10.7554/eLife.46924.011
DOI:
10.7554/eLife.46924.013
DOI:
10.7554/eLife.46924.016
DOI:
10.7554/eLife.46924.014
DOI:
10.7554/eLife.46924.015
DOI:
10.7554/eLife.46924.017
DOI:
10.7554/eLife.46924.020
DOI:
10.7554/eLife.46924.018
DOI:
10.7554/eLife.46924.019
DOI:
10.7554/eLife.46924.021
DOI:
10.7554/eLife.46924.026
DOI:
10.7554/eLife.46924.022
DOI:
10.7554/eLife.46924.023
DOI:
10.7554/eLife.46924.024
DOI:
10.7554/eLife.46924.025
DOI:
10.7554/eLife.46924.027
DOI:
10.7554/eLife.46924.028
DOI:
10.7554/eLife.46924.029
DOI:
10.7554/eLife.46924.030
DOI:
10.7554/eLife.46924.031
DOI:
10.7554/eLife.46924.035
DOI:
10.7554/eLife.46924.036
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2019
detail.hit.zdb_id:
2687154-3
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