Progression Of Neurodegenerative Diseases Research Articles

Amperometry and Electron Microscopy show Stress Granules Induce Homotypic Fusion of Catecholamine Vesicles

AbstractAn overreactive stress granule (SG) pathway and long‐lived, stable SGs formation are thought to participate in the progress of neurodegenerative diseases (NDs). To understand if and how SGs contribute to disorders of neurotransmitter release in NDs, we examined the interaction between extracellular isolated SGs and vesicles. Amperometry shows that the vesicular content increases and dynamics of vesicle opening slow down after vesicles are treated with SGs, suggesting larger vesicles are formed. Data from transmission electron microscopy (TEM) clearly shows that a portion of large dense‐core vesicles (LDCVs) with double/multiple cores appear, thus confirming that SGs induce homotypic fusion between LDCVs. This might be a protective step to help cells to survive following high oxidative stress. A hypothetical mechanism is proposed whereby enriched mRNA or protein in the shell of SGs is likely to bind intrinsically disordered protein (IDP) regions of vesicle associated membrane protein (VAMP) driving a disrupted membrane between two closely buddled vesicles to fuse with each other to form double‐core vesicles. Our results show that SGs induce homotypic fusion of LDCVs, providing better understanding of how SGs intervene in pathological processes and opening a new direction to investigations of SGs involved neurodegenerative disease.

Emerging Roles of Extracelluar Vesicles Derived from Bacteria, Mammalian or Plant Cells in the Pathogenesis and Clinical Application of Neurodegenerative Diseases.

A growing number of studies have indicated that extracellular vesicles (EVs), such as exosomes, are involved in the development of neurodegenerative diseases. Components of EVs with biological effects like proteins, nucleic acids, or other molecules can be delivered to recipient cells to mediate physio-/pathological processes. For instance, some aggregate-prone proteins, such as β-amyloid and α-synuclein, had been found to propagate through exosomes. Therefore, either an increase of detrimental molecules or a decrease of beneficial molecules enwrapped in EVs may fully or partly indicate disease progression. Numerous studies have demonstrated that dysbiosis of the gut microbiota and neurodegeneration are tightly correlated, well-known as the "gut-brain axis". Accumulating evidence has revealed that the gut bacteria-derived EVs play a pivotal role in mediating microbe-host interactions and affect the function of the "gut-brain axis", which subsequently contributes to the pathogenesis of neurodegenerative diseases. In this review, we first briefly discuss the role of EVs from mammalian cells and microbes in mediating the progression of neurodegenerative diseases, and then propose a novel strategy that employs EVs of plants (plant cell-derived exosome-like nanoparticles) for treating neurodegeneration.

Relationship Between Oral Health and Glaucoma Traits in the United Kingdom.

In this cross-sectional analysis of UK Biobank participants, we find no adverse association between self-reported oral health conditions and either glaucoma or elevated intraocular pressures. Poor oral health may cause inflammation, which accelerates the progression of neurodegenerative diseases. We investigated the relationship between oral health and glaucoma. United Kingdom Biobank participants. This is a cross-sectional analysis of participants categorized by self-reported oral health status. Multivariable linear and logistic regression models were used. Primary analysis examined the association with glaucoma prevalence. Secondary analyses examined associations with IOP, macular retinal nerve fiber layer (mRNFL), and ganglion cell inner plexiform layer (mGCIPL) thicknesses, and interaction terms with multitrait glaucoma polygenic risk scores (MTAG PRS) or intraocular pressure (IOP) PRS. A total of 170,815 participants (34.3%) reported current oral health problems, including painful or bleeding gums, toothache, loose teeth, and/or denture wear. A In all, 33,059, 33,004, 14,652, and 14,613 participants were available for analysis of glaucoma, IOP, mRNFL, and mGCIPL, respectively. No association between oral health and glaucoma was identified [odds ratio (OR): 1.04, 95% CI: 0.95-1.14]. IOPs were slightly lower among those with oral disease (-0.08mm Hg, 95% CI: -0.15, -0.009); specifically, among those with loose teeth ( P =0.03) and denture-wearers ( P <0.0001). mRNFL measurements were lower among those with oral health conditions (-0.14 μm, 95% CI: -0.27, -0.0009), but mGCIPL measurements ( P =0.96) were not significantly different. A PRS for IOP or glaucoma did not modify relations between oral health and IOP or glaucoma ( P for interactions ≥​​​​0.17). Self-reported oral health was not associated with elevated IOP or an increased risk of glaucoma. Future studies should confirm the null association between clinically diagnosed oral health conditions and glaucoma.

Endoplasmic reticulum stress and its role in various neurodegenerative diseases

The Endoplasmic reticulum (ER), a critical cellular organelle, maintains cellular homeostasis by regulating calcium levels and orchestrating essential functions such as protein synthesis, folding, and lipid production. A pivotal aspect of ER function is its role in protein quality control. When misfolded proteins accumulate within the ER due to factors like protein folding chaperone dysfunction, toxicity, oxidative stress, or inflammation, it triggers the Unfolded protein response (UPR). The UPR involves the activation of chaperones like calnexin, calreticulin, glucose-regulating protein 78 (GRP78), and Glucose-regulating protein 94 (GRP94), along with oxidoreductases like protein disulphide isomerases (PDIs). Cells employ the Endoplasmic reticulum-associated degradation (ERAD) mechanism to counteract protein misfolding. ERAD disruption causes the detachment of GRP78 from transmembrane proteins, initiating a cascade involving Inositol-requiring kinase/endoribonuclease 1 (IRE1), Activating transcription factor 6 (ATF6), and Protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathways. The accumulation and deposition of misfolded proteins within the cell are hallmarks of numerous neurodegenerative diseases. These aberrant proteins disrupt normal neuronal signalling and contribute to impaired cellular homeostasis, including oxidative stress and compromised protein degradation pathways. In essence, ER stress is defined as the cellular response to the accumulation of misfolded proteins in the endoplasmic reticulum, encompassing a series of signalling pathways and molecular events that aim to restore cellular homeostasis. This comprehensive review explores ER stress and its profound implications for the pathogenesis and progression of neurodegenerative diseases.

Abstract 2386 The role of Hsp90 and its accompanying co-chaperones in the folding of proteins and progression of neurodegenerative diseases

Abstract 2386 The role of Hsp90 and its accompanying co-chaperones in the folding of proteins and progression of neurodegenerative diseases

Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4-mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron-dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism-related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron-dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double-edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy-ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4-mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy-ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases.

Changes in the Expression of Proteins Associated with Neurodegeneration in the Brains of Mice after Infection with Influenza A Virus with Wild Type and Truncated NS1.

Influenza type A virus (IAV) infection is a major cause of morbidity and mortality during influenza epidemics. Recently, a specific link between IAV infection and neurodegenerative disease progression has been established. The non-structural NS1 protein of IAV regulates viral replication during infection and antagonizes host antiviral responses, contributing to influenza virulence. In the present study, we have prepared a mouse lung-to-lung adapted to the NS1-truncated virus (NS80ad). Transcriptome analysis of the gene expression in the lungs revealed that infection with wild-type A/WSN/33 (WSN), NS80, and NS80ad viruses resulted in different regulation of genes involved in signaling pathways associated with the cell proliferation, inflammatory response, and development of neurodegenerative diseases. NS1 protein did not influence the genes involved in the RIG-I-like receptor signaling pathway in the brains. Lethal infection with IAVs dysregulated expression of proteins associated with the development of neurodegenerative diseases (CX3CL1/Fractalkine, Coagulation factor III, and CD105/Endoglin, CD54/ICAM-1, insulin-like growth factor-binding protein (IGFBP)-2, IGFBP-5, IGFBP-6, chitinase 3-like 1 (CHI3L1), Myeloperoxidase (MPO), Osteopontin (OPN), cystatin C, and LDL R). Transcription of GATA3 mRNA was decreased, and expression of MPO was inhibited in the brain infected with NS80 and NS80ad viruses. In addition, the truncation of NS1 protein led to reduced expression of IGFBP-2, CHI3L1, MPO, and LDL-R proteins in the brains. Our results indicate that the influenza virus influences the expression of proteins involved in brain function, and this might occur mostly through the NS1 protein. These findings suggest that the abovementioned proteins represent a promising target for the development of potentially effective immunotherapy against neurodegeneration.

Staging of progressive supranuclear palsy-Richardson syndrome using MRI brain charts for the human lifespan.

Brain charts for the human lifespan have been recently proposed to build dynamic models of brain anatomy in normal aging and various neurological conditions. They offer new possibilities to quantify neuroanatomical changes from preclinical stages to death, where longitudinal MRI data are not available. In this study, we used brain charts to model the progression of brain atrophy in progressive supranuclear palsy-Richardson syndrome. We combined multiple datasets (n = 8170 quality controlled MRI of healthy subjects from 22 cohorts covering the entire lifespan, and n = 62 MRI of progressive supranuclear palsy-Richardson syndrome patients from the Four Repeat Tauopathy Neuroimaging Initiative (4RTNI)) to extrapolate lifetime volumetric models of healthy and progressive supranuclear palsy-Richardson syndrome brain structures. We then mapped in time and space the sequential divergence between healthy and progressive supranuclear palsy-Richardson syndrome charts. We found six major consecutive stages of atrophy progression: (i) ventral diencephalon (including subthalamic nuclei, substantia nigra, and red nuclei), (ii) pallidum, (iii) brainstem, striatum and amygdala, (iv) thalamus, (v) frontal lobe, and (vi) occipital lobe. The three structures with the most severe atrophy over time were the thalamus, followed by the pallidum and the brainstem. These results match the neuropathological staging of tauopathy progression in progressive supranuclear palsy-Richardson syndrome, where the pathology is supposed to start in the pallido-nigro-luysian system and spreads rostrally via the striatum and the amygdala to the cerebral cortex, and caudally to the brainstem. This study supports the use of brain charts for the human lifespan to study the progression of neurodegenerative diseases, especially in the absence of specific biomarkers as in PSP.

Particulate matter from car exhaust alters function of human iPSC-derived microglia

BackgroundAir pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer’s disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia.ResultsHere we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml−1 increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production.ConclusionsOur study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.

Astroglial activation: Current concepts and future directions.

Astrocytes are abundantly and ubiquitously expressed cell types with diverse functions throughout the central nervous system. Astrocytes show remarkable plasticity and exhibit morphological, molecular, and functional remodeling in response to injury, disease, or infection of the central nervous system, as evident in neurodegenerative diseases. Astroglial mediated inflammation plays a prominent role in the pathogenesis of neurodegenerative diseases. This review focus on the role of astrocytes as essential players in neuroinflammation and discuss their morphological and functional heterogeneity in the normal central nervous system and explore the spatial and temporal variations in astroglial phenotypes observed under different disease conditions. This review discusses the intimate relationship of astrocytes to pathological hallmarks of neurodegenerative diseases. Finally, this review considers the putative therapeutic strategies that can be deployed to modulate the astroglial functions in neurodegenerative diseases. HIGHLIGHTS: Astroglia mediated neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. Activated astrocytes exhibit diverse phenotypes in a region-specific manner in brain and interact with β-amyloid, tau, and α-synuclein species as well as with microglia and neuronal circuits. Activated astrocytes are likely to influence the trajectory of disease progression of neurodegenerative diseases, as determined by the stage of disease, individual susceptibility, and state of astroglial priming. Modulation of astroglial activation may be a therapeutic strategy at various stages in the trajectory of neurodegenerative diseases to modify the disease course.

Abstract TP27: Transcriptional and Functional Characterization of Microglia in Vascular Dementia

Introduction: Proper function of the brain relies on sufficient blood supply to meet local energy demand. Age-related pathologies like cerebral small vessel disease (cSVD) compromise the ability of blood vessels to meet local energy demands and lead, over time, to the development of vascular dementia (VaD). Microglia are essential for maintaining homeostasis and have been shown to exacerbate inflammation and disease progression in neurodegenerative diseases. Activated microglia are present in the white matter lesions of human post-mortem VaD brains. However, their role in VaD progression is poorly understood. Hypothesis: Our main objective is to identify microglial pathways that contribute to VaD. We hypothesize microglial dysregulation interferes with brain homeostasis and wound healing, ultimately contributing to disease progression. Methods: Post-mortem samples of periventricular white matter from male and female elderly individuals exhibiting brain pathology consistent with VaD (n=4), along with age- and sex-matched controls without VaD (n=4) were acquired from the NIH NeuroBioBank. We performed single-nuclei RNA sequencing followed by differential gene expression analysis using Seurat and downstream analyses using Ingenuity Pathway Analysis. Results: Over 30,000 nuclei were analyzed. Transcriptomic results reveal profound differences in the microglial transcriptome in VaD, with 690 differentially regulated genes in microglia between cases and controls. Genes related to pathways such as complement production, phagocytosis, macrophage activation and overall protein production are downregulated in VaD while IL-10 production is upregulated (Figure 1B). Conclusions: Our data suggests microglia in VaD adopt a unique transcriptional signature, distinct from that observed in disease-associated microglia in other neurodegenerative conditions, which may impact their ability to maintain homeostasis in VaD.

Vitamin D as a Modulator of Neuroinflammation: Implications for Brain Health.

Neuroinflammation represents a critical immune response within the brain, playing a pivotal role in defense against injury and infection. However, when this response becomes chronic, it can contribute to the development of various neurodegenerative and psychiatric disorders. This bibliographic review delves into the role of vitamin D in modulating neuroinflammation and its implications for brain health, particularly in the context of neurological and psychiatric disorders. While vitamin D is traditionally associated with calcium homeostasis and bone health, it also exerts immunomodulatory and neuroprotective effects within the central nervous system. Through comprehensive analysis of preclinical and clinical studies, we uncover how vitamin D, acting through its receptors in glial cells, may influence the production of proinflammatory cytokines and antioxidants, potentially mitigating the cascade of events leading to neuronal damage. Clinical research has identified vitamin D deficiency as a common thread in the increased risks of multiple sclerosis, Parkinson's disease, Alzheimer's, and depression, among others. Furthermore, preclinical models suggest vitamin D's regulatory capacity over inflammatory mediators, its protective role against neuronal apoptosis, and its contribution to neurogenesis and synaptic plasticity. These insights underscore the potential of vitamin D supplementation not only in slowing the progression of neurodegenerative diseases but also in improving the quality of life for patients suffering from psychiatric conditions. Future clinical studies are essential to validate these findings and further our understanding of vitamin D's capacity to prevent or alleviate symptoms, opening new avenues for therapeutic strategies against neuroinflammation-related pathologies. Neuroinflammation is a crucial immune response in the brain against injuries or infections, but its persistence can lead to diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and depression. Cholecalciferol (Vitamin D3) emerges as a regulator of neuroinflammation, present in brain cells such as astrocytes and microglia, modulating immune function. Vitamin D's mechanisms of action include cytokine modulation and regulation of nuclear and mitochondrial genes. It adjusts inflammatory mediators and antioxidants, resulting in neuroprotective effects. Additionally, vitamin D impacts neurotransmitter synthesis and brain plasticity. This positions vitamin D as a potential adjunct in treating diseases like Alzheimer's and Parkinson's. Lastly, its role in intestinal microbiota and serotonin synthesis contributes to psychiatric disorders like schizophrenia and depression. Thus, vitamin D presents a novel therapeutic approach for neuroinflammatory, neurodegenerative, and neuropsychiatric diseases.

A Review on the Role of Neuroplasticity in Neurodegenerative Disorders and Its Possible Pharmacological and Non-Pharmacological Interventions

Neuroplasticity is the capability of brain cells to interchange as well as modify for the ultimate cause of higher proficiency to acclimatize to the new situations. Neuroplasticity also plays a very pivotal role in the development and then further progressing of neurodegenerative disorders. The severe adjustments in neural plasticity caused by high pressure, anxiety and other terrible stimuli like stress play a considerable role in the onset and cause of depression. This comprehensive review explores the pivotal role of neuroplasticity in neurodegenerative disorders, shedding light on the dynamic adaptive processes of the nervous system in response to pathological conditions. The paper synthesizes current research findings to elucidate the intricate interplay between neuroplasticity and the progression of neurodegenerative diseases. Furthermore, it delves into potential pharmacological and non-pharmacological interventions aimed at modulating neuroplasticity to ameliorate or mitigate the impact of these disorders. By examining diverse strategies, from pharmaceutical interventions to lifestyle modifications, this review contributes to a nuanced understanding of the multifaceted mechanisms underlying neurodegeneration and offers insights into promising avenues for therapeutic development.

Data-driven modelling of neurodegenerative disease progression: thinking outside the black box.

Data-driven disease progression models are an emerging set of computational tools that reconstruct disease timelines for long-term chronic diseases, providing unique insights into disease processes and their underlying mechanisms. Such methods combine a priori human knowledge and assumptions with large-scale data processing and parameter estimation to infer long-term disease trajectories from short-term data. In contrast to 'black box' machine learning tools, data-driven disease progression models typically require fewer data and are inherently interpretable, thereby aiding disease understanding in addition to enabling classification, prediction and stratification. In this Review, we place the current landscape of data-driven disease progression models in a general framework and discuss their enhanced utility for constructing a disease timeline compared with wider machine learning tools that construct static disease profiles. We review the insights they have enabled across multiple neurodegenerative diseases, notably Alzheimer disease, for applications such as determining temporal trajectories of disease biomarkers, testing hypotheses about disease mechanisms and uncovering disease subtypes. We outline key areas for technological development and translation to a broader range of neuroscience and non-neuroscience applications. Finally, we discuss potential pathways and barriers to integrating disease progression models into clinical practice and trial settings.

The function of previously unappreciated exerkines secreted by muscle in regulation of neurodegenerative diseases.

The initiation and progression of neurodegenerative diseases (NDs), distinguished by compromised nervous system integrity, profoundly disrupt the quality of life of patients, concurrently exerting a considerable strain on both the economy and the social healthcare infrastructure. Exercise has demonstrated its potential as both an effective preventive intervention and a rehabilitation approach among the emerging therapeutics targeting NDs. As the largest secretory organ, skeletal muscle possesses the capacity to secrete myokines, and these myokines can partially improve the prognosis of NDs by mediating the muscle-brain axis. Besides the well-studied exerkines, which are secreted by skeletal muscle during exercise that pivotally exert their beneficial function, the physiological function of novel exerkines, e.g., apelin, kynurenic acid (KYNA), and lactate have been underappreciated previously. Herein, this review discusses the roles of these novel exerkines and their mechanisms in regulating the progression and improvement of NDs, especially the significance of their functions in improving NDs' prognoses through exercise. Furthermore, several myokines with potential implications in ameliorating ND progression are proposed as the future direction for investigation. Elucidation of the function of exerkines secreted by skeletal muscle in the regulation of NDs advances the understanding of its pathogenesis and facilitates the development of therapeutics that intervene in these processes to cure NDs.

Analysis of Human Peripheral Blood Mononuclear Cells in Patients with Neurodegenerative Diseases.

The role of immune system in the progression of neurodegenerative diseases has been studied for decades in animal models. However, invasive studies in human subjects remain controversial due to the heterogeneity of the presentation of different diagnostic categories at different stages of the disease. Peripheral blood mononuclear cells (PBMCs) contain immune cells including dendritic cells (DCs), monocytes, macrophages, and T lymphocytes. Isolating PBMCs from whole blood samples collected from patients provides a minimally invasive method for analyzing the immune system's function in patients with neurodegenerative diseases. By isolating single cell types from patients' peripheral blood, in vitro analyses can be conducted including RNA sequencing, immunofluorescence, and phagocytic analysis. In this chapter, we discuss PBMC separation and isolation of macrophages in pure culture in vitro. We also outline methods for performing RNA-seq on cultured macrophages and other techniques for investigating the role of macrophages in neurodegenerative disease pathophysiology.

A histidine-functionalized ROS scavenging hybrid nanozyme for therapeutic application in Parkinson's disease pathogenesis

(1) Functionalized NPs mimic the SOD1 enzyme and demonstrate robust nanozyme activity. (2) Nanozyme exhibits mitochondrial localization and maintains redox homeostasis. (3) Nanozyme inhibits Parkinson’s Disease progression through anti-apoptotic function.

SV2A PET imaging in human neurodegenerative diseases.

This manuscript presents a thorough review of synaptic vesicle glycoprotein 2A (SV2A) as a biomarker for synaptic integrity using Positron Emission Tomography (PET) in neurodegenerative diseases. Synaptic pathology, characterized by synaptic loss, has been linked to various brain diseases. Therefore, there is a need for a minimally invasive approach to measuring synaptic density in living human patients. Several radiotracers targeting synaptic vesicle protein 2A (SV2A) have been created and effectively adapted for use in human subjects through PET scans. SV2A is an integral glycoprotein found in the membranes of synaptic vesicles in all synaptic terminals and is widely distributed throughout the brain. The review delves into the development of SV2A-specific PET radiotracers, highlighting their advancements and limitations in neurodegenerative diseases. Among these tracers, 11C-UCB-J is the most used so far. We summarize and discuss an increasing body of research that compares measurements of synaptic density using SV2A PET with other established indicators of neurodegenerative diseases, including cognitive performance and radiological findings, thus providing a comprehensive analysis of SV2A's effectiveness and reliability as a diagnostic tool in contrast to traditional markers. Although the literature overall suggests the promise of SV2A as a diagnostic and therapeutic monitoring tool, uncertainties persist regarding the superiority of SV2A as a biomarker compared to other available markers. The review also underscores the paucity of studies characterizing SV2A distribution and loss in human brain tissue from patients with neurodegenerative diseases, emphasizing the need to generate quantitative neuropathological maps of SV2A density in cases with neurodegenerative diseases to fully harness the potential of SV2A PET imaging in clinical settings. We conclude by outlining future research directions, stressing the importance of integrating SV2A PET imaging with other biomarkers and clinical assessments and the need for longitudinal studies to track SV2A changes throughout neurodegenerative disease progression, which could lead to breakthroughs in early diagnosis and the evaluation of new treatments.

Catalytic physiological amyloids.

Amyloid fibrils have been identified in many protein systems, mostly linked to progression and cytotoxicity in neurodegenerative diseases and other pathologies, but have also been observed in normal physiological systems. A growing body of work has shown that amyloid fibrils can catalyze chemical reactions. Most studies have focused on catalysis by de-novo synthetic amyloid-like peptides; however, recent studies reveal that physiological, native amyloids are catalytic as well. Here, we discuss methodologies and major experimental aspects pertaining to physiological catalytic amyloids. We highlight analyzes of kinetic parameters related to the catalytic activities of amyloid fibrils, structure-function considerations, characterization of the catalytic active sites, and deciphering of catalytic mechanisms.

CCOG Web-Based Cognitive Assessment Tool.

Cognitive testing is an essential part of clinical diagnostics and clinical trials in Alzheimer's disease. Digital cognitive tests hold a great opportunity to provide more versatile and cost-efficient patient pathways through flexible testing including at home. In this work, we describe a web-based cognitive test, cCOG, that can be used in screening, differential diagnosis, and monitoring the progression of neurodegenerative diseases.