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@ARTICLE{LamannaRama:307448,
author = {N. Lamanna-Rama and M. Casquero-Veiga and C. Ceron and G.
Sobrino and I. Fernandez-Nueda and S. Kossatz$^*$ and D.
Sehlin and M. Desco and B. Salinas and M. Cortes-Canteli},
title = {{A}lzheimer's {I}maging {C}onsortium.},
journal = {Alzheimer's and dementia},
volume = {21 Suppl 8},
number = {Suppl 8},
issn = {1552-5260},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DKFZ-2025-03047},
pages = {e109958},
year = {2025},
note = {Poster presentation / PMID: 41434183},
abstract = {Alzheimer's disease (AD) is the most common form of
dementia[1]. Despite the advances in the understanding of
its main neuropathological hallmarks, a significant gap
remains in comprehending this multifactorial
neurodegenerative disorder. Contributing factors to AD
include chronic vascular dysregulation and a prothrombotic
milieu, promoting fibrin accumulation in brain vessels[2].
Fibrin, the main protein component of blood clots, is
significantly increased in $60\%$ of AD-patients' brains[3].
Furthermore, its strong interaction with amyloid-β promotes
the production of degradation-resistant clots[2]. This
prothrombotic milieu intensifies hypoperfusion,
neurodegeneration and blood-brain barrier (BBB)
disruption[4], but not in all patients. Early detection
could help identify patients which might benefit from
anticoagulant therapies[5]. The BioClotAD Project aims to
develop an imaging biomarker based on a fibrin binding probe
(FBP)[6] to non-invasively identify AD's pro-coagulant
state.BioClotAD involves four partners in three European
countries with complementary expertise, using extensive in
vitro, ex vivoand in vivo assays, including AD animal models
and human AD brain samples. Our project is based on three
blocks: 1) Testing the FBP to in vivo detect the cerebral
occlusions by nuclear imaging. 2) Detecting fibrin deposits
inside the brain parenchyma with FBP coupled to a
transferrin receptor antibody (FBP-TfR) to facilitate BBB
crossing[7]. FBP-TfR will be labelled for optical and
nuclear imaging. 3) Validating the most promising FBP probes
in frozen brain samples of AD patients by autoradiography or
fluorescence microscopy.BioClotAD provides feasible
neuroimaging strategies to in vivo detect the fibrin
cerebral accumulation of AD models and identify the specific
regional distribution in the brain. Our project will set the
basis for future clinical trials on neuroimaging of the
cerebral fibrin accumulation in AD.BioClotAD neuroimaging
biomarkers will allow the early detection of the
pro-thrombotic state in AD, opening a window of opportunity
to delay the disease progression by personalized
anticoagulant therapies. References: 1. Alzheimer's
Association. 2021.
https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf.
2. Cortes-Canteli et al. 2020. 10.1016/j.jacc.2019.10.062 3.
Cortes-Canteli, et al. 2015.
https://doi.org/10.1016/j.neurobiolaging.2014.10.030 4.
Cortes-Canteli, et al. 2012.
https://doi.org/10.3233/JAD-2012-120820 5. Cortes-Canteli,
et al. 2019. https://doi.org/10.1016/j.jacc.2019.07.081 6.
Oliveira, Caravan. 2017. https://doi.org/10.1039/c7dt02634j
7. Sehlin, et al. 2019.
https://doi.org/10.1007/s00259-019-04426-0.},
subtyp = {Other},
keywords = {Humans / Alzheimer Disease: diagnostic imaging / Alzheimer
Disease: metabolism / Alzheimer Disease: pathology / Animals
/ Fibrin: metabolism / Brain: diagnostic imaging / Brain:
metabolism / Brain: pathology / Biomarkers / Disease Models,
Animal / Fibrin (NLM Chemicals) / Biomarkers (NLM
Chemicals)},
cin = {MU01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41434183},
pmc = {pmc:PMC12726136},
doi = {10.1002/alz70862_109958},
url = {https://inrepo02.dkfz.de/record/307448},
}