TY  - JOUR
AU  - Levites, Yona
AU  - Dammer, Eric B
AU  - Ran, Yong
AU  - Tsering, Wangchen
AU  - Duong, Duc
AU  - Abreha, Measho
AU  - Gadhavi, Joshna
AU  - Lolo, Kiara
AU  - Trejo-Lopez, Jorge
AU  - Phillips, Jennifer
AU  - Iturbe, Andrea
AU  - Erquizi, Aya
AU  - Moore, Brenda D
AU  - Ryu, Danny
AU  - Natu, Aditya
AU  - Dillon, Kristy
AU  - Torrellas, Jose
AU  - Moran, Corey
AU  - Ladd, Thomas
AU  - Afroz, Farhana
AU  - Islam, Tariful
AU  - Jagirdar, Jaishree
AU  - Funk, Cory C
AU  - Robinson, Max
AU  - Rangaraju, Srikant
AU  - Borchelt, David R
AU  - Ertekin-Taner, Nilüfer
AU  - Kelly, Jeffrey W
AU  - Heppner, Frank L
AU  - Johnson, Erik C B
AU  - McFarland, Karen
AU  - Levey, Allan I
AU  - Prokop, Stefan
AU  - Seyfried, Nicholas T
AU  - Golde, Todd E
TI  - Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer's disease.
JO  - Cell reports / Medicine
VL  - 5
IS  - 8
SN  - 2666-3791
CY  - Maryland Heights, MO
PB  - Elsevier
M1  - DZNE-2024-01058
SP  - 101669
PY  - 2024
AB  - 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.
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: genetics
KW  - Proteomics: methods
KW  - Animals
KW  - Amyloid beta-Peptides: metabolism
KW  - Humans
KW  - Plaque, Amyloid: metabolism
KW  - Plaque, Amyloid: pathology
KW  - Mice
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Proteome: metabolism
KW  - Mice, Transgenic
KW  - Carrier Proteins: metabolism
KW  - Carrier Proteins: genetics
KW  - Cytokines: metabolism
KW  - Male
KW  - Alzheimer’s disease (Other)
KW  - Midkine (Other)
KW  - Pleiotrophin (Other)
KW  - aggregation (Other)
KW  - amyloid (Other)
KW  - animal models (Other)
KW  - plaques (Other)
KW  - proteomics (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Proteome (NLM Chemicals)
KW  - pleiotrophin (NLM Chemicals)
KW  - Carrier Proteins (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11384960
C6  - pmid:39127040
DO  - DOI:10.1016/j.xcrm.2024.101669
UR  - https://pub.dzne.de/record/271706
ER  -