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Thiazine Red(+) platelet inclusions in Cerebral Blood Vessels are first signs in
an Alzheimer s Disease mouse model
#MMPMID27345467
Kniewallner KM
; Wenzel D
; Humpel C
Sci Rep
2016[Jun]; 6
(?): 28447
PMID27345467
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Strong evidence shows an association between cerebral vascular diseases and
Alzheimer´s disease (AD). In order to study the interaction of beta-amyloid (A?)
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 A? 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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