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Publication : Thiazine Red(+) platelet inclusions in Cerebral Blood Vessels are first signs in an Alzheimer's Disease mouse model.

First Author  Kniewallner KM Year  2016
Journal  Sci Rep Volume  6
Pages  28447 PubMed ID  27345467
Mgi Jnum  J:264931 Mgi Id  MGI:6198785
Doi  10.1038/srep28447 Citation  Kniewallner KM, et al. (2016) Thiazine Red(+) platelet inclusions in Cerebral Blood Vessels are first signs in an Alzheimer's Disease mouse model. Sci Rep 6:28447
abstractText  Strong evidence shows an association between cerebral vascular diseases and Alzheimer s disease (AD). In order to study the interaction of beta-amyloid (Abeta) plaques with brain vessels, we crossbred an AD mouse model (overexpressing amyloid precursor protein with the Swedish-Dutch-Iowa mutations, APP_SweDI) with mice expressing green fluorescent protein (GFP) under the flt-1/VEGFR1 promoter in vessels (GFP_FLT1). Our data show, that only very few Abeta plaques were seen in 4-months old mice, focused in the mammillary body and in the lateral septal nucleus. The number of plaques markedly increased with age being most prominent in 12-months old mice. Thiazine Red was used to verify the plaques. Several Thiazine Red(+) inclusions were found in GFP(+) vessels, but only in non-perfused 4-months old mice. These inclusions were verified by Resorufin stainings possibly representing cerebral amyloid angiopathy. The inclusions were also seen in non-crossbred APP_SweDI but not in wildtype and GFP_FLT1 mice. In order to characterize these inclusions Flow Cytometry (FACS) analysis demonstrated that platelets were specifically stained by Thiazine Red(+), more pronounced when aggregated. In conclusion, our data show that Thiazine Red(+) inclusions representing aggregated platelets are a first pathological sign in AD before plaque development and may become important therapeutic targets in early AD.
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