BACKGROUND: Alzheimer\'s disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes. Preclinical research has shown that GLP-1 receptor agonists decrease neuroinflammation, tau phosphorylation, amyloid deposition, synaptic function, and memory formation. Phase 2 and 3 studies are now occurring in Alzheimer\'s disease populations. In this article, we present a detailed assessment of the therapeutic potential of GLP-1 analogues and DPP4 inhibitors in Alzheimer\'s disease.
OBJECTIVE: This study aimed to gain insight into how GLP-1 analogues and associated antagonists of DPP4 safeguard against AD.
METHODS: This study uses terms from search engines, such as Scopus, PubMed, and Google Scholar, to explore the role, function, and treatment options of the GLP-1 analogue for AD.
RESULTS: The review suggested that GLP-1 analogues may be useful for treating AD because they have been linked to anti-inflammatory, neurotrophic, and neuroprotective characteristics. Throughout this review, we discuss the underlying causes of AD and how GLP signaling functions.
CONCLUSIONS: With a focus on AD, the molecular and pharmacological effects of a few GLP-1/GIP analogs, both synthetic and natural, as well as DPP4 inhibitors, have been mentioned, which are in the preclinical and clinical studies. This has been demonstrated to improve cognitive function in Alzheimer\'s patients.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder resulting from the deposition of misfolded and neurotoxic forms of tau protein in specific areas of the midbrain, basal ganglia, and cortex. It is one of the most representative forms of tauopathy. PSP presents in several different phenotypic variations and is often accompanied by the development of concurrent neurodegenerative disorders. PSP is universally fatal, and effective disease-modifying therapies for PSP have not yet been identified. Several tau-targeting treatment modalities, including vaccines, monoclonal antibodies, and microtubule-stabilizing agents, have been investigated and have had no efficacy. The need to treat PSP and other tauopathies is critical, and many clinical trials investigating tau-targeted treatments are underway. In this review, the PubMed database was queried to collect information about preclinical and clinical research on PSP treatment. Additionally, the US National Library of Medicine\'s ClinicalTrials.gov website was queried to identify past and ongoing clinical trials relevant to PSP treatment. This narrative review summarizes our findings regarding these reports, which include potential disease-modifying drug trials, modifiable risk factor management, and symptom treatments.

Cerebrospinal fluid (CSF) phosphorylated tau231 (P-tau231) is associated with neuropathological outcomes of Alzheimer\'s disease (AD). The invasive access of cerebrospinal fluid has greatly stimulated interest in the identification of blood-based P-tau231, and the recent advent of single-molecule array assay for the quantification of plasma P-tau231 may provide a turning point to evaluate the usefulness of P-tau231 as an AD-related biomarker. Yet, in the plasma P-tau231 literature, findings with regard to its diagnostic utility have been inconsistent, and thus, we aimed to statistically investigate the potential of plasma P-tau231 in the context of AD via meta-analysis. Publications on plasma P-tau231 were systematically retrieved from PubMed, EMBASE, the Cochrane library and Web of Science databases. A total of 10 studies covering 2007 participants were included, and we conducted random-effect or fixed-effect meta-analysis, sensitivity analysis and publication bias analysis using the STATA SE 14.0 software. According to our quantitative integration, plasma P-tau231 increased from cognitively unimpaired (CU) populations to mild cognitive impairment to AD and showed significant changes in pairwise comparisons of AD, mild cognitive impairment and CU. Plasma P-tau231 level was significantly higher in CU controls with positive amyloid-β (Aβ) status compared with Aβ-negative CU group. Additionally, the excellent diagnostic accuracy of plasma P-tau231 for asymptomatic Aβ pathology was verified by the pooled value of area under the receiver operating characteristic curves (standard mean difference [95% confidence interval]: .75 [.69, .81], P < 0.00001). Overall, the increased plasma P-tau231 concentrations were found in relation to the early development and progression of AD.

Alzheimer\'s disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD. Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Multiple cellular processes synergistically promote hypoxia, including aging, hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, and traumatic brain injury. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Treatments targeting hypoxia may delay or mitigate the progression of AD. Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD. Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism, tau phosphorylation, neuroinflammation, neuronal apoptosis, oxidative stress, neurotrophic factors, mitochondrial function, cerebral blood volume, and protein synthesis. In this review, we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations. We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

UNASSIGNED: Ketamine is an established intervention for treatment-resistant depression (TRD). However, long-term adverse effects with repeated doses remain insufficiently characterized. Although several animal models have shown N-methyl-D-aspartate glutamate receptor antagonists to produce various neuropathological reactions, attention surrounding the risk of brain lesions has been minimal.
UNASSIGNED: The current review focuses on potential neuropathological changes associated with ketamine. Search terms included variations of ketamine, Olney lesions, tau hyperphosphorylation, and parvalbumin interneurons.
UNASSIGNED: Daily high-dose ketamine use in substance use disorder (SUD) populations was associated with clear neurotoxic effects, while no studies specifically evaluated effects of ketamine protocols used for TRD. It is difficult to discern effects directly attributable to ketamine due to methodological factors, such as comorbidities and dramatic differences in dose in SUD populations versus infrequent sub-anesthetic doses typically prescribed for TRD. Taken together, animal models and human ketamine SUD populations suggest potential neuropathology with chronic high-dose ketamine exposure exceeding those recommended for adults with TRD. It is unknown whether repeat sub-anesthetic dosing of ketamine in adults with TRD is associated with Olney lesions or other neuropathologies. In the interim, practitioners should be vigilant for this possibility recognizing that the condition itself is associated with neurodegenerative processes.