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@ARTICLE{Levites:271706,
author = {Levites, Yona and Dammer, Eric B and Ran, Yong and Tsering,
Wangchen and Duong, Duc and Abreha, Measho and Gadhavi,
Joshna and Lolo, Kiara and Trejo-Lopez, Jorge and Phillips,
Jennifer and Iturbe, Andrea and Erquizi, Aya and Moore,
Brenda D and Ryu, Danny and Natu, Aditya and Dillon, Kristy
and Torrellas, Jose and Moran, Corey and Ladd, Thomas and
Afroz, Farhana and Islam, Tariful and Jagirdar, Jaishree and
Funk, Cory C and Robinson, Max and Rangaraju, Srikant and
Borchelt, David R and Ertekin-Taner, Nilüfer and Kelly,
Jeffrey W and Heppner, Frank L and Johnson, Erik C B and
McFarland, Karen and Levey, Allan I and Prokop, Stefan and
Seyfried, Nicholas T and Golde, Todd E},
title = {{I}ntegrative proteomics identifies a conserved {A}β
amyloid responsome, novel plaque proteins, and pathology
modifiers in {A}lzheimer's disease.},
journal = {Cell reports / Medicine},
volume = {5},
number = {8},
issn = {2666-3791},
address = {Maryland Heights, MO},
publisher = {Elsevier},
reportid = {DZNE-2024-01058},
pages = {101669},
year = {2024},
abstract = {Alzheimer's disease (AD) is a complex neurodegenerative
disorder that develops over decades. AD brain proteomics
reveals vast alterations in protein levels and numerous
altered biologic pathways. Here, we compare AD brain
proteome and network changes with the brain proteomes of
amyloid β (Aβ)-depositing mice to identify conserved and
divergent protein networks with the conserved networks
identifying an Aβ amyloid responsome. Proteins in the most
conserved network (M42) accumulate in plaques,
cerebrovascular amyloid (CAA), and/or dystrophic neuronal
processes, and overexpression of two M42 proteins, midkine
(Mdk) and pleiotrophin (PTN), increases the accumulation of
Aβ in plaques and CAA. M42 proteins bind amyloid fibrils in
vitro, and MDK and PTN co-accumulate with cardiac
transthyretin amyloid. M42 proteins appear intimately linked
to amyloid deposition and can regulate amyloid deposition,
suggesting that they are pathology modifiers and thus
putative therapeutic targets. We posit that
amyloid-scaffolded accumulation of numerous M42+ proteins is
a central mechanism mediating downstream pathophysiology in
AD.},
keywords = {Alzheimer Disease: metabolism / Alzheimer Disease:
pathology / Alzheimer Disease: genetics / Proteomics:
methods / Animals / Amyloid beta-Peptides: metabolism /
Humans / Plaque, Amyloid: metabolism / Plaque, Amyloid:
pathology / Mice / Brain: metabolism / Brain: pathology /
Proteome: metabolism / Mice, Transgenic / Carrier Proteins:
metabolism / Carrier Proteins: genetics / Cytokines:
metabolism / Male / Alzheimer’s disease (Other) / Midkine
(Other) / Pleiotrophin (Other) / aggregation (Other) /
amyloid (Other) / animal models (Other) / plaques (Other) /
proteomics (Other) / Amyloid beta-Peptides (NLM Chemicals) /
Proteome (NLM Chemicals) / pleiotrophin (NLM Chemicals) /
Carrier Proteins (NLM Chemicals) / Cytokines (NLM
Chemicals)},
cin = {AG Heppner},
ddc = {610},
cid = {I:(DE-2719)1810007},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11384960},
pubmed = {pmid:39127040},
doi = {10.1016/j.xcrm.2024.101669},
url = {https://pub.dzne.de/record/271706},
}