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Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer's disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer's disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators' levels. In addition, a suppression by half was observed in the levels of both Aβ aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension.

Introduction: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) represent two major chronic diseases that affect a large percentage of the population and share common pathogenetic mechanisms, including oxidative stress and inflammation. Considering their common mechanistic aspects, and given the current lack of effective therapies for AD, accumulating research has focused on the therapeutic potential of antidiabetic drugs in the treatment or prevention of AD., Areas Covered: This review examines the latest preclinical and clinical evidence on the potential of antidiabetic drugs as candidates for AD treatment. Numerous approved drugs for T2DM, including insulin, metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium glucose cotransporter 2 inhibitors (SGLT2i), are in the spotlight and may constitute novel approaches for AD treatment., Expert Opinion: Among other pharmacologic agents, GLP-1 RA and SGLT2i have so far exhibited promising results as novel treatment approaches for AD, while current research has centered on deciphering their action on the central nervous system (CNS). Further investigation is crucial to reveal the most effective pharmacological agents and their optimal combinations, maximize their beneficial effects on neurons, and find ways to increase their distribution to the CNS.

Elderly cats develop age-related behavioral and neuropathological changes that ultimately lead to cognitive dysfunction syndrome (CDS). These neuropathologies share similarities to those seen in the brains of humans with Alzheimer's disease (AD), including the extracellular accumulation of ß -amyloid (Aβ) and intraneuronal deposits of hyperphosphorylated tau, which are considered to be the two major hallmarks of AD. The present study assessed the presence and distribution of Aβ and tau hyperphosphorylation within the cat brain ( n = 55 cats), and how the distribution of these proteins changes with age and the presence of CDS. For this, immunohistochemistry was performed on seven brain regions from cats of various ages, with and without CDS ( n = 10 with CDS). Cats accumulate both intracytoplasmic and extracellular deposits of Aβ, as well as intranuclear and intracytoplasmic hyperphosphorylated tau deposits. Large extracellular aggregates of Aβ were found in elderly cats, mainly in the cortical brain areas, with occasional hippocampal aggregates. This may suggest that these aggregates start in cortical areas and later progress to the hippocampus. While Aβ senile plaques in people with AD have a dense core, extracellular Aβ deposits in cats exhibited a diffuse pattern, similar to the early stages of plaque pathogenesis. Intraneuronal Aβ deposits were also observed, occurring predominantly in cortical brain regions of younger cats, while older cats had few to no intraneuronal Aβ deposits, especially when extracellular aggregates were abundant. Intracytoplasmic hyperphosphorylated tau was found within neurons in the brains of elderly cats, particularly in those with CDS. Due to their ultrastructural features, these deposits are considered to be pre-tangles, which are an early stage of the neurofibrillary tangles seen in AD. The largest numbers of pre-tangles are found mainly in the cerebral cortex of elderly cats, whereas lower numbers were found in other regions (i.e., entorhinal cortex and hippocampus). For the first time, intranuclear tau was found in both phosphorylated and non-phosphorylated states within neurons in the cat brain. The highest numbers of intranuclear deposits were found in the cortex of younger cats, and this tended to decrease with age. In contrast, elderly cats with pre-tangles had only occasional or no nuclear labelling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sordo, Martini, Houston, Head and Gunn-Moore.)

The present study provided an investigation of associations between leisure activity and early Alzheimer's disease neuropathology (i.e., brain β-amyloid) and episodic memory in a sample of 65 adults with Down syndrome (aged 30-53 years), at baseline and follow-up, approximately three years apart. Findings indicated that leisure activity at baseline was not associated with brain β-amyloid at baseline or change in brain β-amyloid from baseline to follow-up. Greater cognitively stimulating leisure activity at baseline was associated with better episodic memory at baseline, and greater social leisure activity at baseline was associated with less decline in episodic memory from baseline to follow-up. High (as opposed to low) levels of social and overall leisure activity at baseline moderated the association between increase in brain β-amyloid and decline in episodic memory, from baseline to follow-up. Findings suggest that cognitively stimulating and social leisure activity could protect against the effect of Alzheimer's disease neuropathology on episodic memory in adults with Down syndrome., (© 2019 Wiley Periodicals, Inc.)

Alzheimer's disease is the most prevalent neurodegenerative pathology. According to the amyloid cascade hypothesis, a key event of the Alzheimer's disease pathogenesis is a transition of the β-amyloid peptide (Аβ) from the monomeric form to the aggregated state. The mechanism of Аβ aggregation is intensively studied in vitro, by means of synthetic peptides and various physico-chemical methods allowing evaluation of size, molecular structure, and morphology of the formed aggregates. The paper reviews both the well-known and recently introduced physico-chemical methods for analysis of Аβ aggregation, including microscopу, optical and fluorescent methods, method of electron paramagnetic resonance, electrochemical and electrophoretic methods, gel-filtration, and mass spectrometric methods. Merits and drawbacks of the methods are discussed. The unique possibility to simultaneously observe Аβ monomers as well oligomers and large aggregates by means of atomic force microscopy or fluorescence correlation spectroscopy is emphasized. The high detection sensitivity of the latter method, monitoring the aggregation process in Аβ solutions at low peptide concentrations is underlined. Among mass spectrometric methods, the ion mobility mass spectrometry is marked out as a method enabling to obtain information about both the spectrum of Аβ oligomers and their structure. It is pointed out that the use of several methods giving the complementary data about Аβ aggregates is the best experimental approach to studying the process of b-amyloid peptide aggregation in vitro.