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Medin amyloid forms age‐associated aggregates in the brain vasculature and may contribute to cerebral β‐amyloidosis
Author(s) -
Wagner Jessica,
Degenhardt Karoline,
Wild Katleen,
Obermüller Ulrike,
Haesler Lisa M.,
Koppelmann Anna Julia,
von Zweydorf Felix,
Gloeckner Christian Johannes,
Maxwell Rusheka,
Rotermund Carola,
Skodras Angelos,
Madine Jillian,
Davies Hannah A.,
Del Turco Domenico,
Deller Thomas,
Kahle Philipp J.,
Jucker Mathias,
Neher Jonas J.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.042861
Subject(s) - amyloidosis , amyloid (mycology) , pathology , genetically modified mouse , population , human brain , neuroscience , biology , medicine , transgene , biochemistry , gene , environmental health
Background The most common human amyloid is probably medin (AMed), which deposits in the aorta of nearly everyone above 50 years of age. Previous studies reported that medin amyloid may co‐aggregate and seed serum amyloid A. Because of this finding and its exceedingly high prevalence in the aging population, we studied whether medin aggregates form in the brain during aging and may interact with other age‐associated amyloids such as Aβ. Method In order to study the pathobiology of medin amyloid and its contribution to vascular and parenchymal amyloidosis, we first investigated the occurrence of medin in wildtype mice. Additionally, we used APP transgenic mouse lines and human tissue for immuno‐histochemical and immunoprecipitation experiments to study a potential protein‐protein interaction with Aβ. Result We find that medin deposits are prevalent in the human brain vasculature and seem to increase both with age and Aβ pathology. Moreover, co‐immunoprecipitation experiments indicate an interaction of Aβ and medin. Strikingly, we also observe that, similar to the human situation, amyloid‐like deposits of medin are formed in the aorta as well as in the brain vasculature of aging wildtype mice. Further experiments in APP transgenic mice showed that medin does not only co‐localize with Aβ Plaques and CAA, but may also promote cerebral β‐amyloidosis in mouse models of Alzheimer’s pathology. Conclusion Our findings suggest that age‐associated medin deposition occurs both in the mouse and human brain, where it may promote cerebral β‐amyloidosis.