Children's weight status and parental perception in Croatia.

The predominant form of dementia is Alzheimer’s disease (AD), which manifests chiefly as progressive deficits in learning and memory []. Patients with AD develop extracellular senile plaques comprising amyloid beta (Aβ) and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau []. Aβ/tau pathologies cause cognitive impairment in AD pathoprogression by exacerbating glial activation and the excessive release of proinflammatory mediators []. Despite active efforts to develop disease-modifying drugs for AD, there is no AD therapeutic that can successfully regulate the various pathological symptoms of AD []. Most AD therapeutics target a single AD pathology, such as Aβ, tau, the cholinergic system, or neuroinflammation, which may explain their limited therapeutic efficacy. Therefore, multitarget drugs could be a successful strategies for treating AD. Abemaciclib mesylate is an inhibitor of cyclin-dependent kinase 4 (CDK4) and CDK6, and is approved by the FDA for treatment of HR-( +) and HER2-(−) breast cancer []. Interestingly, abemaciclib is also a potent inhibitor of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), which is involved in AD-related pathoprogression, including neuroinflammation, cognitive function, and/or Aβ and tau pathology []. This dual inhibition of CDK4/6 and DYRK1A implies that abemaciclib might modulate AD pathologies, and we previously demonstrated that abemaciclib treatment improves cognitive function and reduces Aβ/tau pathology and neuroinflammatory responses in 3- to 4-month-old and 6-month-old 5xFAD mice (early and intermediate stages of AD) and 3- to 4-month-old human mutant P301S tau transgenic (PS19) mice (early stage of tauopathy) []. In addition, a recent study further reported that abemaciclib treatment attenuates tau pathology through CDK4/6-independent inhibition of tau kinases (e.g., CaMKII and GSK3β) in App/MAPT knock-in mice, an AD model []. Here, we extend our previous work by examining the impact of abemaciclib treatment on neuroinflammation and memory function in 6- and 9-month-old PS19 mice. Six-month-old PS19 mice were intraperitoneally (i.p.) injected with vehicle (10% DMSO) or abemaciclib (30 mg/kg) daily for 17 days. Subsequent immunofluorescence staining with anti-Iba-1 and anti-GFAP antibodies showed that abemaciclib administration significantly reduced Iba-1 fluorescence intensity in the hippocampal CA1 and Iba-1-labeled area in the entorhinal cortex (EC) in 6-month-old PS19 mice (Fig. A–C). Furthermore, abemaciclib treatment significantly decreased GFAP fluorescence intensity and GFAP-labeled area in the EC but not the hippocampus of 6-month-old PS19 mice (Fig. D–F). These data indicate that abemaciclib treatment partially diminishes microglial/astroglial activation and hypertrophy in 6-month-old PS19 mice. The region-specific effect of abemaciclib on astrocytic activation may be due to regional differences in blood–brain barrier permeability or in the expression and activity of abemaciclib targets (e.g., DYRK1A, CDK4/6, CaMKII, and GSK3β).