Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease.

TitleIdentification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsMann AP, Scodeller P, Hussain S, Braun GB, Mölder T, Toome K, Ambasudhan R, Teesalu T, Lipton SA, Ruoslahti E
JournalNat Commun
Volume8
Issue1
Pagination1403
Date Published2017 Nov 10
ISSN2041-1723
Abstract

Cerebrovascular changes occur in Alzheimer's disease (AD). Using in vivo phage display, we searched for molecular markers of the neurovascular unit, including endothelial cells and astrocytes, in mouse models of AD. We identified a cyclic peptide, CDAGRKQKC (DAG), that accumulates in the hippocampus of hAPP-J20 mice at different ages. Intravenously injected DAG peptide homes to neurovascular unit endothelial cells and to reactive astrocytes in mouse models of AD. We identified connective tissue growth factor (CTGF), a matricellular protein that is highly expressed in the brain of individuals with AD and in mouse models, as the target of the DAG peptide. We also showed that exogenously delivered DAG homes to the brain in mouse models of glioblastoma, traumatic brain injury, and Parkinson's disease. DAG may potentially be used as a tool to enhance delivery of therapeutics and imaging agents to sites of vascular changes and astrogliosis in diseases associated with neuroinflammation.

DOI10.1038/s41467-017-01096-0
Alternate JournalNat Commun
PubMed ID29123083
PubMed Central IDPMC5680235
Grant ListP30 NS076411 / NS / NINDS NIH HHS / United States
P30 CA030199 / CA / NCI NIH HHS / United States
R01 NS086890 / NS / NINDS NIH HHS / United States
DP1 DA041722 / DA / NIDA NIH HHS / United States
P01 HD029587 / HD / NICHD NIH HHS / United States
/ / Wellcome Trust / United Kingdom