Current Alzheimer Research - Volume 17, Issue 4, 2020

Pathologic calcium (Ca2+) signaling linked to Alzheimer’s Disease (AD) involves the intracellular Ca2+ release channels/ryanodine receptors (RyRs). RyRs are macromolecular complexes where the protein-protein interactions between RyRs and several regulatory proteins impact the channel function. Pharmacological and genetic approaches link the destabilization of RyRs macromolecular complexes to several human patholo Read More

Alzheimer’s Disease (AD), a neurodegenerative disorder with high incidence and mortality, is leading its way to the top of the list of the deadliest diseases without an effective disease-modifying drug. Ca2+ dysregulation, specifically abnormal release of Ca2+ via over activated ryanodine receptor (RyR), has been increasingly considered as an alternative upstream mechanism in AD pathology. Consequently, dantrolene, a R Read More

Mitochondria absorb calcium (Ca2+) at the expense of the electrochemical gradient generated during respiration. The influx of Ca2+ into the mitochondrial matrix helps maintain metabolic function and results in increased cytosolic Ca2+ during intracellular Ca2+ signaling. Mitochondrial Ca2+ homeostasis is tightly regulated by proteins located in the inner and outer mitochondrial membranes and by the cross-talk with en Read More

Despite decades of research and effort, there is still no effective disease-modifying treatment for Alzheimer’s Disease (AD). Most of the recent AD clinical trials were targeting amyloid pathway, but all these trials failed. Although amyloid pathology is a hallmark and defining feature of AD, targeting the amyloid pathway has been very challenging due to low efficacy and serious side effects. Alternative approaches or mecha Read More

Background: β-Site APP-cleaving enzyme 1 (BACE1) is a key enzyme involved in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and Mild Cognitive Impairment (MCI). We aimed to investigate the potential associations of plasma BACE1 levels and BACE1 gene polymorphism with different cognitive performances in T2DM patients with MCI. Methods: The recruited 186 T2DM subjects were divided into 92 MCI group Read More

Background: Sedentary life-style is a significant public health issue. It increases the incidence of type-2 diabetes mellitus (DM2) and systemic arterial hypertension (SAH), which in turn may impair physical and mental health. In fact, disrupted glucose metabolism is characteristic of Alzheimer’s dementia, and it is often dubbed as type-3 diabetes. Objective: The purpose of this study was to assess the level of activity, Read More

Background: Subjective Memory Impairment (SMI) may tremendously increase the risk of Alzheimer’s Disease (AD). The full understanding of the neuromechanism of SMI will shed light on the early intervention of AD. Methods: In the current study, 23 Healthy Controls (HC), 22 SMI subjects and 24 amnestic Mild Cognitive Impairment (aMCI) subjects underwent the comprehensive neuropsychological assessment and the resting-s Read More

Background: Cognitive capacities in Alzheimer’s Disease (AD) are impaired by an epigenetic blockade mediated by histone deacetylase 2 (HDAC2), which prevents the transcription of genes that are important for synaptic plasticity. Objective: Investigation of the functional relationship between cell adhesion molecule L1 and HDAC2 in AD. Methods: Cultures of dissociated cortical and hippocampal neurons from wild-type or L1-de Read More

Background: Anti-amyloid-β (Aβ) monoclonal antibodies (mAbs) are currently in development for treating Alzheimer’s disease. Objectives: To address the complexity of Aβ target engagement profiles, improve the understanding of crenezumab Pharmacokinetics (PK) and Aβ Pharmacodynamics (PD) in the brain, and facilitate comparison of anti-Aβ therapies with different binding characteristics. Methods: A m Read More