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Excessive local host-graft connectivity in aging and amyloid-loaded brain.
Sci. Adv. 8:eabg9287 (2022)
Transplantation is a clinically relevant approach for brain repair, but much remains to be understood about influences of the disease environment on transplant connectivity. To explore the effect of amyloid pathology in Alzheimer's disease (AD) and aging, we examined graft connectivity using monosynaptic rabies virus tracing in APP/PS1 mice and in 16- to 18-month-old wild-type (WT) mice. Transplanted neurons differentiated within 4 weeks and integrated well into the host visual cortex, receiving input from the appropriate brain regions for this area. Unexpectedly, we found a prominent several-fold increase in local inputs, in both amyloid-loaded and aged environments. State-of-the-art deep proteome analysis using mass spectrometry highlights complement system activation as a common denominator of environments promoting excessive local input connectivity. These data therefore reveal the key role of the host pathology in shaping the input connectome, calling for caution in extrapolating results from one pathological condition to another.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2022
HGF-reported in Year
2022
ISSN (print) / ISBN
2375-2548
e-ISSN
2375-2548
Journal
Science Advances
Quellenangaben
Volume: 8,
Issue: 23,
Article Number: eabg9287
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
Washington, DC [u.a.]
Reviewing status
Peer reviewed
POF-Topic(s)
30204 - Cell Programming and Repair
30203 - Molecular Targets and Therapies
30203 - Molecular Targets and Therapies
Research field(s)
Stem Cell and Neuroscience
Enabling and Novel Technologies
Enabling and Novel Technologies
PSP Element(s)
G-500800-001
G-505700-001
A-630700-001
G-505700-001
A-630700-001
WOS ID
WOS:000852717800001
Scopus ID
85131904143
PubMed ID
35687689
Erfassungsdatum
2022-07-08