Drug Development.

Background: The Apolipoprotein E4 isoform (ApoE4), encoded by the APOE gene, stands out as the most influential genetic factor in late-onset Alzheimer's disease (LOAD). The ApoE4 isoform contributes to metabolic and neuropathological abnormalities during brain aging, with a strong correlation observed in APOE4-positive Alzheimer's disease cases between phosphorylated tau burden and amyloid deposition. Despite compelling evidence of APOE-mediated neuroinflammation influencing the progression of tau-mediated neurodegeneration, the molecular mechanisms underlying these phenomena remain largely unknown.

Drug Development.

Background: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.

Drug Development.

Background: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.

Drug Development.

Background: Parkinson's disease is an hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid-brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Filgrastim has been reported to produce anti-oxidant, anti-inflammatory and neuromodulatory actions in previous studies.

Drug Development.

Background: Accumulation of amyloid beta 42 (Aβ42) senile plaques is the most critical event leading to Alzheimer's disease (AD). Currently approved drugs for AD have not been able to effectively modify the disease. This has caused increasing research interests in health beneficial nutritious plant foods as viable alternative therapy to prevent or manage AD.

Drug Development.

Background: Alzheimer's disease (AD) is the most prevalent cause of dementia accounting for an estimated 60% to 80% of cases. Despite advances in the research field, developing truly effective therapies for AD symptoms remains a major challenge. Sweet almond contain nutrients that have the potential of combating age-related brain dysfunction, by improving learning, memory and neurocognitive performance.

Drug Development.

Background: Only about 50% of the variance in cognitive decline occurring during Alzheimer's pathogenesis is attributable to standard AD biomarkers (cerebrocortical Aβ, pathological tau, and atrophy) (Tosun et al., Alzheimer's Dement. 18: 1370, 2022).

Drug Development.

Background: Alzheimer's Disease (AD) is the leading form of senile dementia, affecting ∼6 million Americans and having a national economic impact of $321 billion, numbers expected to double by 2050. The major pathological hallmarks of AD include Amyloid Beta (Aβ) plaques and Tau neurofibrillary tangles (NFT). The first goal of this research was to develop novel forms of carbon dots (CD) using various precursors.

Drug Development.

Background: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).

Method: We performed comprehensive human genetic and multi-omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first-in-class, picomolar sEH inhibitor) in a transgenic mouse model of AD-5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons.

Drug Development.

Background: The spatiotemporal pattern of the spread of pathologically modified tau through brain regions in Alzheimer's disease (AD) can be explained by prion-like cell-to-cell seeding and propagation of misfolded tau aggregates. Hence, to develop targeted therapeutic antibodies, it is important to identify the seeding- and propagation-competent tau species. The hexapeptide VQIINK of tau is a critical region for tau aggregation, and K280 is acetylated in various tauopathies including AD.

Drug Development.

Background: Epidemiological studies report an elevated risk of neurodegenerative disorders, particularly Parkinson's disease (PD), in patients with type 2 diabetes mellitus (T2DM) that is mitigated in those prescribed incretin mimetics or dipeptidyl peptidase 4 inhibitors (DPP-4Is). Incretin mimetic repurposing appears promising in human PD and Alzheimer's disease (AD) clinical trials. DPP-4Is are yet to be evaluated in PD or AD human studies.

Drug Development.

Background: In recent decades, epidemiological and experimental studies have looked into the role of pesticides, particularly the herbicide paraquat, in the development of Parkinson's disease. Horseradish tree (Moringa oleifera) is an ethnobotanical plant with lots of therapeutic potential, but there is a dearth of information on the bioactive properties of the seed alkaloid extracts.

Method: This study examined the modulatory effects of various concentrations of an alkaloid extract from the seeds of Horseradish Tree (Moringa oleifera) on the survival rate of flies exposed to paraquat, as well as certain biochemical and molecular markers related to Parkinson's disease in the heads of the flies.

Drug Development.

Background: Individuals with type 2 diabetes mellitus (T2DM) face an increased risk of dementia. Recent discoveries indicate that SGLT2 inhibitors, a newer class of anti-diabetic medication, exhibit beneficial metabolic effects beyond glucose control, offering a potential avenue for mitigating the risk of Alzheimer's disease (AD). However, limited evidence exists regarding whether the use of SGLT2 inhibitors effectively reduces the risk of AD.

Drug Development.

Background: Abnormal aggregation and accumulation of tau is a hallmark of tauopathy including Alzheimer's disease. Effective targeting of tau for therapeutic purposes requires a clear understanding of its epitope landscape with identification of a key pathogenic tau species. Despite numerous proposed and tested tau epitopes, ranging from the N-terminus to the microtubule-binding region and C-terminus, the most effective target remains elusive.

Drug Development.

Background: The well-accepted statistical efficacy inference approach for Alzheimer's disease (AD) clinical trials compares the absolute difference in change from baseline at the last study visit using MMRM (henceforth referred to as MMRM-Last-Visit). Recent AD clinical trials have shown that treatment effects may be manifested prior to 18 months. The objective is to evaluate models estimating an overall treatment effect across all post-baseline visits that may characterize disease modifying effects in contemporary early AD clinical trials.

Drug Development.

Background: The impact of probiotics as gut and immunological modulator in restoring gut microbial balance and immune cells expression have generated much attention in the health sector. Its inhibitory effect on bacterial translocation and associated neural inflammatory processes has been reported. However, there is scarcity of data on its neuroprotective impact against neuroinflammation-associated neurodegeneration and memory impairment.

Drug Development.

Background: Cyclin Y (CCNY) is a member of cyclin protein family inhibiting long-term synaptic plasticity, which is related to the learning and memory function in neuronal system. Recently, CCNY has been reported to associate with the cognitive deficits in Alzheimer's disease (AD).

Method: In this study, we discovered PFTAIRE peptide to diminish CCNY protein level and to ameliorate cognitive dysfunction in AD.

Drug Development.

Background: As amyloid-β (Aβ) aggregates are considered as the biomarkers and key factors in the pathology of Alzheimer's disease, there has been extensive investigation into Aβ-targeting compounds for the development of diagnostics and drug discovery related to the disorder. However, the polymorphic and heterogenous nature of Aβ aggregates impedes the structural understanding of their structure. Consequently it is a major challenge to develop new diagnostic and therapeutic development of AD and to study the mechanism of Aβ-targeting compounds.

Drug Development.

Dementia patients often received one clinical diagnosis, yet most of these cases present multiple underlying pathologies. Bringing the transition from clinical-based to biological-based diagnosis holds promise with the diagnostic criteria proposed by the Alzheimer's Association (AA) Revised Criteria for Diagnosis and Staging of Alzheimer's Disease and the Neuronal Synuclein Disease Integrated Staging System (NSD-ISS). This session aims to explore the practical implications of the AA revised criteria for diagnosing and designing clinical trials in Lewy body disease (LBD).

Drug Development.

Background: In preparation for therapeutic trails involving patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), there is a need for valid, disease-specific caregiver-reported outcome (CRO) measures capable of tracking symptomatic burden in response to therapy over time. CROs are useful tools in clinical trials for individuals with AD, MCI, and dementia who are unable to self-report. In addition, CROs are accepted by the United States Food and Drug Administration to support regulatory claims.

Drug Development.

Background: Several studies have shown the influential role of nutraceuticals on cognition and mental functions. Dihydroxytrimethoxyflavone, a natural flavone found in herbal drugs, is documented to be neuroprotective in different model systems. Nevertheless, possible memory improvement effects of dihydroxytrimethoxyflavone via nuclear factor-E2-related factor 2 (Nrf2) (a crucial regulator of antioxidative system) has not been systematically evaluated.

Drug Development.

Background: Some types of cancer have been associated with reduced risk of clinical dementia diagnosis. Whether cancer history may be associated with neuropathological features of neurodegeneration or cerebrovascular disease is not well understood. We investigated the relation between cancer diagnosis and brain pathology in a sample of community-based research volunteers enrolled in an Alzheimer's Disease Research Center (ADRC) cohort.

Drug Development.

Background: Effective early intervention of mild cognitive impairment (MCI) is the key for preventing dementia. However, there is currently no drug for MCI. As a multi-targeted neuroprotective agent, butylphthalide has been demonstrated to repair cognition in patients with vascular cognitive impairment, and has the potential to treat MCI due to Alzheimer's disease (AD).

Drug Development.

Background: Recruitment registries are tools to decrease the time and cost required to identify and enroll eligible participants into clinical research. Despite their potential to increase the efficiency of accrual, few analyses have assessed registry effectiveness. We investigated the outcomes of study referrals from the Consent-to-Contact (C2C) registry, a recruitment registry at the University of California, Irvine.

Drug Development.

Background: Studies suggest a potential link between stroke and Alzheimer's disease wherein stroke may serve as a trigger for the onset or acceleration of Alzheimer's pathogenesis as damage to the brain's blood vessels may lead to the accumulation of amyloid beta protein which is a hallmark of Alzheimer's disease. Recent research has shown that stroke treatment may hold the key to treating Alzheimer's disease. The anti-inflammatory potentials of Cholinergic signaling are a novel therapeutic target in memory decline associated with Alzheimer's.