Alzheimer’s disease (AD) is increasingly associated with alterations in cholesterol metabolism. Proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme regulating low-density lipoprotein receptor (LDLR) degradation, has been implicated in AD through mechanisms involving amyloid-β (Aβ) processing, tau phosphorylation, and synaptic dysfunction. This review aimed to evaluate clinical, genetic, and experimental evidence regarding the role of PCSK9 in AD and its potential as a biomarker or therapeutic target. A systematic search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar (2020–2025) using predefined terms related to PCSK9 and Alzheimer’s disease. Eligible studies included clinical, in vivo, and in vitro investigations reporting PCSK9 expression, regulation, or inhibition in relation to AD pathology. Due to methodological heterogeneity, a narrative synthesis was performed. Forty-two studies met inclusion criteria. Preclinical findings consistently showed that elevated PCSK9 may indirectly promote Aβ accumulation, tau hyperphosphorylation, neuroinflammation, and cognitive decline, while genetic deletion or pharmacological inhibition of PCSK9 mitigates these effects. Clinical evidence was variable: several studies identified increased PCSK9 levels in cerebrospinal fluid or brain tissue of AD patients, often correlating with tau markers, but large-scale genetic and Mendelian randomization studies did not confirm a causal association. PCSK9 inhibitors, widely used in cardiovascular therapy, demonstrated potent LDL-C reduction without cognitive adverse effects. Experimental data suggest that PCSK9 contributes to AD-related pathology, whereas human evidence indicates a modulatory or biomarker role rather than a causative one. Despite strong preclinical data, human genetics lacks causal evidence for PCSK9 in Alzheimer’s. It may be a disease modifier or biomarker; its clinical relevance requires confirmation through longitudinal studies and CNS-penetrant therapies.

Aspartame is widely used artificial sweetener. However, chronic exposure to aspartame led to spatial memory impairment and elevated oxidative stress in the brain. Extract of turmeric rhizome (Curcuma longa) (TUR) and extract of bitter melon (Momordica charantia) (BM) is known to have antioxidant activity. The present study was aimed to examine the neuroprotective potential of TUR and BM extracts, either as single or as combination, against the effects of aspartame in the brain. Here, Sprague-Dawley rats fed with aspartame (40 mg/kg BW) for 28 days were compared with rats fed with extract and aspartame. To assess neuroprotective potential, rats were given extract 7 days before and during aspartame treatment. Spatial memory was assessed with Morris water maze test followed with H&E staining of hippocampal region. Brain lipid peroxidation and enzymatic activity of malondialdehyde (MDA), glutathione peroxidase (GPx), and Acetylcholinesterase (AChE) were measured to probe status of oxidative stress in the brain. Aspartame-treated rats demonstrated spatial memory impairment and reduced number of hippocampal cells and elevated levels of MDA, downregulated activity of GPx and elevated activity of AChE. In contrast, animals received both aspartame and extract demonstrated better spatial memory function, higher number of hippocampal areas, increased GPX activity, reduced MDA levels, and decreased AChE activity were observed in the brain of extract-treated rats. Taken together, our results suggest that extract of TUR rhizome and BM fruit exhibit antioxidant activity which may contribute to the neuroprotective effects against aspartame-induced memory impairment in rats.

Objective: Aspartame (ASP) consumption in various food and beverage products has generated a lot of controversy on safety. Many reports, ASP caused deterioration of health condition likes diabetes, psychiatric disorders, memory loss, etc. This study aimed to investigate the optimization duration of ASP to induce memory loss in Sprague Dawley rats. Methods: The ASP was administered 40 mg/kg BW orally for 28 days in rats. Analysis of memory loss by neurobehavioural changes including latency time, length of track, per cent time and frequency target quadrant using Morris Water Maze (MWM) at day 14, 21, 28, and 24 hours after the last treatment. Results: The administration of ASP showed the time-dependent changes for each indicator of neurobehavioural. The results demonstrated during 28 days of induction showed a significant decrease in latency time, length of track, per cent time and frequency target quadrant. Conclusion: From the results, it can be concluded administration of ASP during 28 days induce neurobehavioural changes related to memory loss in rats. Abstrak: Objektif: Penggunaan aspartame (ASP) sebagai pemanis buatan yang banyak terdapat pada makanan, dan minuman menimbulkan berbagai kontroversi dalam hal keamanan. Berbagai data menunjukkan ASP dapat menyebabkan gangguan kesehatan seperti diabetes, gangguan psikiatrik, penurunan fungsi memori, dll. Penelitian ini bertujuan untuk menentukan waktu durasi penggunaan ASP yang dapat menyebabkan gangguan fungsi memori pada tikus Sprague Dawley. Metode:ASP diberikan secara oral pada tikus dengan dosis 40 mg/kg BB selama 28 hari. Analisis terhadap fungsi memori dilakukan dengan adanya perubahan perilaku pada hewan, meliputi waktu latensi, Panjang lintasan, persentase waktu dan frekuensi kuadran menggunakan Morris Water Maze (MWM) setelah 24 jam setelah pemberian pada hari ke 14,21, 28. Hasil: Pemberian ASP menunjukkan adanya perbedaan waktu pada setiap indicator perilaku. Pemberian selama 28 hari menujukkan adanya perbedaan signifikan pada penurunan waktu latensi, Panjang lintasan, persentase waktu dan frekuensi kuadran. Kesimpulan: Berdasarkan hasil, pemberian ASP selama 28 hari dapat menyebabkan adanya perubahan perilaku yang berkaitan dengan fungsi memori pada tikus.

The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) and its role in promoting the degradation of the low-density lipoprotein receptor (LDLR) has revolutionized lipid-lowering therapy, offering new therapy for patients with hypercholesterolemia. Notably, PCSK9 is now being explored for functions beyond lipid regulation. Emerging evidence implicates PCSK9 in vascular pathology by influencing endothelial dysfunction, inflammatory signaling, oxidative stress, and vascular homeostasis—potentially through LDLR-independent mechanisms. This review critically evaluates PCSK9’s potential as a regulator of endothelial dysfunction, synthesizing findings from in vitro, in vivo, and clinical studies. While current PCSK9-targeted therapies, including monoclonal antibodies and siRNA-based agents, have demonstrated robust efficacy in lowering lipid levels and reducing cardiovascular risk, their direct effects on endothelial PCSK9 signaling remain unclear. On the other hand, novel approaches—such as peptide-based inhibitors, intracellular modulation, and natural compounds—resulted in new insights into endothelial-specific PCSK9 pathways. Overall, this review highlights the need to bridge experimental and clinical evidence by applying endothelial-focused models, multi-omics analyses, and functional vascular assessments to clarify the role of PCSK9 in endothelial dysfunction and to propose future strategies for cardiovascular interventions targeting PCSK9-mediated endothelial dysfunction.

Pre-Dominance Herbs Medicine against Alzheimer’s Disease, In Vivo Studies: A Literature Review

Tuberkulosis (TB) adalah penyakit yang disebabkan oleh Mycobacterium tuberculosis. Pada tahun 2018, jumlah penderita tuberkulosis di dunia sebanyak 10 juta jiwa (kisaran 9,0-11,1 juta) dengan rata-rata global 130 kasus baru per 100.000 penduduk pertahun dan jumlah penderita yang meninggal dunia akibat TB 1,2 juta (kisaran 1,2 - 1,3 juta). Kondisi kasus tuberkulosis di Indonesia sebanyak 511.873 kasus, dengan 4.431 kasus TB resistensi obat dan keberhasilan pengobatan mencapai 85%. Infeksi tuberkulosis dimulai ketika droplet yang mengandung bakteri M. tuberculosis masuk dalam paru-paru bermanifestasi dalam alveolus. Remaja merupakan salah satu fase dalam siklus kehidupan manusia dan merupakan masa transisi dari usia anak-anak ke dewasa. Berbagai masalah kesehatan dapat ditemukan pada remaja di Indonesia. Masalah kesehatan tersebut diantaranya: kehamilan tidak diinginkan dan aborsi, penyakit malaria, TBC, DBD, diare, stunting, thypus abdominalis, IMS, masalah gizi (gizi kurang dan gizi lebih). Berdasarkan data yang diperoleh disekolah SMK Karya Bhakti, Kabupaten Pringsewu, Provinsi Lampung terdapat siswa/i sebanyak 50 orang yang harus diberikan informasi tentang penyakit TBC. Metode digunakan dengan cara memberikan penyuluhan kepada siswa/i, serta tanya jawab. Setelah diberika penyuluhan seluruh siswa/i SMK Karya Bhakti Pringsewu mengerti mengenai penyakit TBC.