Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-? Protein Precursor Transgenic Mice.

ABSTRACT: A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-? (A?) protein in A? Precursor Protein (APP) transgenic mice overexpressing vasculotropic A?. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and A? deposition in the brain using APP transgenic mice. At baseline, 14-month-old female Tg2576 mice were randomly assigned to a control group (vehicle), aspirin group (0.01% aspirin), or cilostazol group (0.01% cilostazol). The severity of cerebral micro-hemorrhages (i.e., number), area of senile plaque, and severity of vascular amyloid burden (quantified with cerebral amyloid angiopathy (CAA) score (=number of A?-positive vessels × severity of amyloid burden of A?-positive vessels) were evaluated in the brain of mice aged 15 and 21-23 months. At 15 months, no differences were shown in each pathological change among the three groups. At 21-23 months, there were no differences in the severity of cerebral micro-hemorrhages or area of senile plaque among the three groups. However, the CAA score was significantly lower in the cilostazol compared to the control group (p = 0.046, Mann-Whitney U test), although no difference was seen between the control and aspirin group. Our study showed that lower-dose cilostazol could reduce the vascular amyloid burden without increasing cerebral micro-hemorrhages in APP transgenic mice.

SUBMITTER: Yakushiji Y 

PROVIDER: S-EPMC7177305 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature