title: Thiazine Red(+) platelet inclusions in Cerebral Blood Vessels are first signs in an Alzheimer's Disease mouse model.
abstract: Strong evidence shows an association between cerebral vascular diseases and Alzheimer´s disease (AD). In order to study the interaction of beta-amyloid (Aβ) 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 Aβ 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.
authors.affiliation: Laboratory of Psychiatry and Exp. Alzheimer's Research, Department of Psychiatry Psychotherapy and Psychosomatik, Medical University of Innsbruck, Austria.
authors.forename: Kathrin M
authors.initials: KM
authors.lastname: Kniewallner
authors.affiliation: Institute of Physiology I, University Hospital Bonn, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Wenzel
authors.affiliation: Laboratory of Psychiatry and Exp. Alzheimer's Research, Department of Psychiatry Psychotherapy and Psychosomatik, Medical University of Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D001808:Blood Vessels / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008326:Mammillary Bodies / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010078:Oxazines / Q000737:chemistry; D058225:Plaque, Amyloid / Q000473:pathology; D010974:Platelet Aggregation; D012686:Septal Nuclei / Q000378:metabolism / Q000473:pathology; D013194:Staining and Labeling; D013843:Thiazines / Q000737:chemistry*
chemical_list: D016564:Amyloid beta-Protein Precursor; D010078:Oxazines; D013843:Thiazines; D049452:Green Fluorescent Proteins; C014180:resorufin