Open AccessAβ oligomers trigger and accelerate Aβ seeding
Author(s) -
Katzmarski Natalie,
ZieglerWaldkirch Stephanie,
Scheffler Nina,
Witt Christian,
AbouAjram Claudia,
Nuscher Brigitte,
Prinz Marco,
Haass Christian,
MeyerLuehmann Melanie
Publication year - 2020
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12734
Subject(s) - seeding , monomer , oligomer , fibril , biophysics , chemistry , genetically modified mouse , immunoprecipitation , amyloid (mycology) , in vivo , protein aggregation , transgene , amyloid β , microbiology and biotechnology , recombinant dna , biochemistry , biology , disease , medicine , pathology , polymer , inorganic chemistry , organic chemistry , gene , agronomy
Aggregation of amyloid‐β (Aβ) that leads to the formation of plaques in Alzheimer's disease (AD) occurs through the stepwise formation of oligomers and fibrils. An earlier onset of aggregation is obtained upon intracerebral injection of Aβ‐containing brain homogenate into human APP transgenic mice that follows a prion‐like seeding mechanism. Immunoprecipitation of these brain extracts with anti‐Aβ oligomer antibodies or passive immunization of the recipient animals abrogated the observed seeding activity, although induced Aβ deposition was still evident. Here, we establish that, together with Aβ monomers, Aβ oligomers trigger the initial phase of Aβ seeding and that the depletion of oligomeric Aβ delays the aggregation process, leading to a transient reduction of seed‐induced Aβ deposits. This work extends the current knowledge about the role of Aβ oligomers beyond its cytotoxic nature by pointing to a role in the initiation of Aβ aggregation in vivo . We conclude that Aβ oligomers are important for the early initiation phase of the seeding process.