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| 001 | 165578 | ||
| 005 | 20240611120548.0 | ||
| 024 | 7 | _ | |a 10.1038/s41586-022-05440-3 |2 doi |
| 024 | 7 | _ | |a pmid:36385530 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC9712113 |2 pmc |
| 024 | 7 | _ | |a 0028-0836 |2 ISSN |
| 024 | 7 | _ | |a 1476-4687 |2 ISSN |
| 024 | 7 | _ | |a altmetric:138511969 |2 altmetric |
| 037 | _ | _ | |a DZNE-2022-01718 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Wagner, Jessica |0 P:(DE-2719)2812193 |b 0 |e First author |
| 245 | _ | _ | |a Medin co-aggregates with vascular amyloid-β in Alzheimer's disease. |
| 260 | _ | _ | |a London [u.a.] |c 2022 |b Nature Publ. Group |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1718022178_5323 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Aggregates of medin amyloid (a fragment of the protein MFG-E8, also known as lactadherin) are found in the vasculature of almost all humans over 50 years of age1,2, making it the most common amyloid currently known. We recently reported that medin also aggregates in blood vessels of ageing wild-type mice, causing cerebrovascular dysfunction3. Here we demonstrate in amyloid-β precursor protein (APP) transgenic mice and in patients with Alzheimer's disease that medin co-localizes with vascular amyloid-β deposits, and that in mice, medin deficiency reduces vascular amyloid-β deposition by half. Moreover, in both the mouse and human brain, MFG-E8 is highly enriched in the vasculature and both MFG-E8 and medin levels increase with the severity of vascular amyloid-β burden. Additionally, analysing data from 566 individuals in the ROSMAP cohort, we find that patients with Alzheimer's disease have higher MFGE8 expression levels, which are attributable to vascular cells and are associated with increased measures of cognitive decline, independent of plaque and tau pathology. Mechanistically, we demonstrate that medin interacts directly with amyloid-β to promote its aggregation, as medin forms heterologous fibrils with amyloid-β, affects amyloid-β fibril structure, and cross-seeds amyloid-β aggregation both in vitro and in vivo. Thus, medin could be a therapeutic target for prevention of vascular damage and cognitive decline resulting from amyloid-β deposition in the blood vessels of the brain. |
| 536 | _ | _ | |a 352 - Disease Mechanisms (POF4-352) |0 G:(DE-HGF)POF4-352 |c POF4-352 |f POF IV |x 0 |
| 536 | _ | _ | |a 354 - Disease Prevention and Healthy Aging (POF4-354) |0 G:(DE-HGF)POF4-354 |c POF4-354 |f POF IV |x 1 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de |
| 650 | _ | 7 | |a Amyloid beta-Peptides |2 NLM Chemicals |
| 650 | _ | 7 | |a Amyloid beta-Protein Precursor |2 NLM Chemicals |
| 650 | _ | 7 | |a Serum Amyloid A Protein |2 NLM Chemicals |
| 650 | _ | 2 | |a Alzheimer Disease: metabolism |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Middle Aged |2 MeSH |
| 650 | _ | 2 | |a Alzheimer Disease |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides |2 MeSH |
| 650 | _ | 2 | |a Cognitive Dysfunction |2 MeSH |
| 650 | _ | 2 | |a Plaque, Amyloid |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Protein Precursor |2 MeSH |
| 650 | _ | 2 | |a Mice, Transgenic |2 MeSH |
| 650 | _ | 2 | |a Serum Amyloid A Protein |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: metabolism |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Protein Precursor: metabolism |2 MeSH |
| 650 | _ | 2 | |a Plaque, Amyloid: metabolism |2 MeSH |
| 650 | _ | 2 | |a tau Proteins: metabolism |2 MeSH |
| 700 | 1 | _ | |a Degenhardt, Karoline |0 P:(DE-2719)2810939 |b 1 |e First author |
| 700 | 1 | _ | |a Veit, Marleen |0 P:(DE-2719)9001638 |b 2 |
| 700 | 1 | _ | |a Louros, Nikolaos |0 0000-0002-4030-1022 |b 3 |
| 700 | 1 | _ | |a Konstantoulea, Katerina |0 0000-0002-0960-6274 |b 4 |
| 700 | 1 | _ | |a Skodras, Angelos |0 P:(DE-2719)2810430 |b 5 |
| 700 | 1 | _ | |a Wild, Katleen |0 P:(DE-2719)2811762 |b 6 |
| 700 | 1 | _ | |a Liu, Ping |0 P:(DE-2719)9002490 |b 7 |u dzne |
| 700 | 1 | _ | |a Obermüller, Ulrike |0 P:(DE-2719)2814201 |b 8 |
| 700 | 1 | _ | |a Bansal, Vikas |0 P:(DE-2719)2812055 |b 9 |
| 700 | 1 | _ | |a Dalmia, Anupriya |0 P:(DE-2719)2812478 |b 10 |
| 700 | 1 | _ | |a Häsler, Lisa M |0 P:(DE-2719)2811581 |b 11 |
| 700 | 1 | _ | |a Lambert, Marius |0 P:(DE-2719)2810762 |b 12 |
| 700 | 1 | _ | |a De Vleeschouwer, Matthias |b 13 |
| 700 | 1 | _ | |a Davies, Hannah A |b 14 |
| 700 | 1 | _ | |a Madine, Jillian |0 0000-0001-9963-5871 |b 15 |
| 700 | 1 | _ | |a Kronenberg-Versteeg, Deborah |0 P:(DE-2719)9001451 |b 16 |
| 700 | 1 | _ | |a Feederle, Regina |0 P:(DE-2719)2812867 |b 17 |
| 700 | 1 | _ | |a Del Turco, Domenico |b 18 |
| 700 | 1 | _ | |a Nilsson, K Peter R |b 19 |
| 700 | 1 | _ | |a Lashley, Tammaryn |b 20 |
| 700 | 1 | _ | |a Deller, Thomas |b 21 |
| 700 | 1 | _ | |a Gearing, Marla |b 22 |
| 700 | 1 | _ | |a Walker, Lary C. |0 P:(DE-2719)9000947 |b 23 |
| 700 | 1 | _ | |a Heutink, Peter |0 P:(DE-2719)2810728 |b 24 |
| 700 | 1 | _ | |a Rousseau, Frederic |0 0000-0002-9189-7399 |b 25 |
| 700 | 1 | _ | |a Schymkowitz, Joost |b 26 |
| 700 | 1 | _ | |a Jucker, Mathias |0 P:(DE-2719)2000010 |b 27 |
| 700 | 1 | _ | |a Neher, Jonas |0 P:(DE-2719)2811021 |b 28 |e Last author |
| 773 | _ | _ | |a 10.1038/s41586-022-05440-3 |g Vol. 612, no. 7938, p. 123 - 131 |0 PERI:(DE-600)1413423-8 |n 7938 |p 123 - 131 |t Nature |v 612 |y 2022 |x 0028-0836 |
| 856 | 4 | _ | |u https://pub.dzne.de/record/165578/files/DZNE-2022-01718.pdf |y OpenAccess |
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