Diagnosis Of Neurodegenerative Diseases Research Articles

Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells.

Calcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA-GNR) conjugated glutamic acid developed in the study was used as a nano-bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA-GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.

Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases.

JOURNAL/nrgr/04.03/01300535-202508000-00027/figure1/v/2024-09-30T120553Z/r/image-tiff Several promising plasma biomarker proteins, such as amyloid-β (Aβ), tau, neurofilament light chain, and glial fibrillary acidic protein, are widely used for the diagnosis of neurodegenerative diseases. However, little is known about the long-term stability of these biomarker proteins in plasma samples stored at -80°C. We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort. Plasma samples from 229 cognitively unimpaired individuals, encompassing healthy controls and those experiencing subjective cognitive decline, as well as 99 patients with cognitive impairment, comprising those with mild cognitive impairment and dementia, were acquired from the Sino Longitudinal Study on Cognitive Decline project. These samples were stored at -80°C for up to 6 years before being used in this study. Our results showed that plasma levels of Aβ42, Aβ40, neurofilament light chain, and glial fibrillary acidic protein were not significantly correlated with sample storage time. However, the level of total tau showed a negative correlation with sample storage time. Notably, in individuals without cognitive impairment, plasma levels of total protein and tau phosphorylated protein threonine 181 (p-tau181)also showed a negative correlation with sample storage time. This was not observed in individuals with cognitive impairment. Consequently, we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time. Therefore, caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases, such as Alzheimer's disease. Furthermore, in cohort studies, it is important to consider the impact of storage time on the overall results.

Exosomes for neurodegenerative diseases: diagnosis and targeted therapy.

Neurodegenerative diseases are still challenging clinical issues, with no curative interventions available and early, accurate diagnosis remaining difficult. Finding solutions to them is of great importance. In this review, we discuss possible exosomal diagnostic biomarkers and explore current explorations in exosome-targeted therapy for some common neurodegenerative diseases, offering insights into the clinical transformation of exosomes in this field. The burgeoning research on exosomes has shed light on their potential applications in disease diagnosis and treatment. As a type of extracellular vesicles, exosomes are capable of crossing the blood - brain barrier and exist in various body fluids, whose components can reflect pathophysiological changes in the brain. In addition, they can deliver specific drugs to brain tissue, and even possess certain therapeutic effects themselves. And the recent advancements in engineering modification technology have further enabled exosomes to selectively target specific sites, facilitating the possibility of targeted therapy for neurodegenerative diseases. The unique properties of exosomes give them great potential in the diagnosis and treatment of neurodegenerative diseases, and provide novel ideas for dealing with such diseases.

Modeling Neurodegeneration and Regeneration in Parkinson's Disease

The diagnosis and prevention of neurodegenerative diseases is a heavily examined topic in the neuroscience discipline. Whether it be from the anatomical and biological perspectives or the psychological and sociological perspectives, the ultimate goal is to discover strategies to pinpoint the infection as soon as possible. This article begins with reviewing the small-world network structure and then combines the sociological and anatomical perspectives to explain the progression of neuronal death within the brain by using rsfMRI data and the Hegselmann-Krause Model of Opinion Dynamics to illustrate critical interactions between brain regions, and to predict the ultimate behavior of the neural network after initial degeneration Following experimentation–in which critical regions related to Parkinson’s Disease were studied–thresholds were identified in specific regions which exhibited consistent converging behavior of the neural network toward either degenerative or regenerative directions. Furthermore, a simple graphical model is proposed to demonstrate the ranges of values in which current brain health could be of concern. We concluded that neuron death in one brain region can lead to further infection in the resulting system; however, some regions can also directly/indirectly compensate for the system’s decreased function. In future research endeavors, this could provide insight into developing more accurate predictive models for the goal of early detection of a diseased brain and its recovery.

Biomarkers of oxidative stress and proteopathies in the diagnosis of neurodegenerative diseases

Introduction. Despite numerous studies in the field of neurodegenerative diseases, the exact mechanisms of these processes have not yet been identified. The purpose of this review is to analyze the methodological approaches necessary to revise the traditional and create new reliable prognostic and diagnostic algorithms that reflect pathogenetic features at different stages of neurodegeneration and atypical course of the disease. Material and methods. The review highlights the results of clinical and experimental studies obtained using a complex of clinical, laboratory and instrumental methods with an emphasis on markers of oxidative stress and proteopathy. In preparing the materials, sources from international and domestic databases were used: Scopus, Web of Science, Pub Medline, RSCI mainly for the last 15 years. Results. An idea has been formed about the molecular mechanisms of neural tissue regression in a number of neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s disease. The relationship between the parameters of the oxidative process and the features of metal-energy shifts in organs and organ systems is demonstrated. The role of markers of oxidative stress in the early stages, when the process of inflammation prevails and in the atypical course of the disease, is shown. Valuable biochemical markers are cytokines, glutathione levels, myeloperoxidase activation, and isoprostanes. The review points to the prospect of including in screening indicators of iron and other metals such as Zn, Mg, affecting the clinic accumulation of β-amyloid, in connection with which they can be considered as the basis for the progression of neurodegeneration. New data on the contribution of halogenating stress to the pathogenesis of neuroinflammation are presented. An aspect requiring development in the field of biomarkers for assessing the duration of the disease and prognostic prospects is the data on the correlation of metabolic shifts in the intestinal microbiota with the duration of the disease and the inflammatory process. Essential for the creation of express diagnostic methods is the determination of redox balance as an integral marker in saliva, which has obvious advantages over the use of biological fluids, such as liquor and serum. Conclusion. The prospects of creating new prognostic and diagnostic schemes are associated with complexes, including laboratory and instrumental methods, in blood, liquor and saliva. Evaluation of the sensitivity and specificity of new markers depending on the clinical diagnosis allows the selection of pathogenetically significant markers in the early stages of the disease, with atypical neurodegeneration, to establish subtypes of the disease, to carry out their differential diagnosis.

The Olfactory Trail of Neurodegenerative Diseases.

Alterations in olfactory functions are proposed as possible early biomarkers of neurodegenerative diseases. Parkinson's and Alzheimer's diseases manifest olfactory dysfunction as a symptom, which is worth mentioning. The alterations do not occur in all patients, but they can serve to rule out neurodegenerative pathologies that are not associated with small deficits. Several prevalent neurodegenerative conditions, including impaired smell, arise in the early stages of Parkinson's and Alzheimer's diseases, presenting an attractive prospect as a snitch for early diagnosis. This review covers the current knowledge on the link between olfactory deficits and Parkinson's and Alzheimer's diseases. The review also covers the emergence of olfactory receptors as actors in the pathophysiology of these diseases. Olfactory receptors are not exclusively expressed in olfactory sensory neurons. Olfactory receptors are widespread in the human body; they are expressed, among others, in the testicles, lungs, intestines, kidneys, skin, heart, and blood cells. Although information on these ectopically expressed olfactory receptors is limited, they appear to be involved in cell recognition, migration, proliferation, wound healing, apoptosis, and exocytosis. Regarding expression in non-chemosensory regions of the central nervous system (CNS), future research should address the role, in both the glia and neurons, of olfactory receptors. Here, we review the limited but relevant information on the altered expression of olfactory receptor genes in Parkinson's and Alzheimer's diseases. By unraveling how olfactory receptor activation is involved in neurodegeneration and identifying links between olfactory structures and neuronal death, valuable information could be gained for early diagnosis and intervention strategies in neurodegenerative diseases.

Neuropathology of the Neurodegenerative Diseases

A definite diagnosis of neurodegenerative diseases is required for neuropathological examination during an autopsy. Each neurodegenerative disease has specific vulnerable regions and affected systems (system degeneration), and is typified by an accumulation of abnormal protein with the formation of characteristic morphological aggregates in the nerve and glial cells, called proteinopathy. The most common neurodegenerative diseases are tauopathy, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD); α-synucleinopathy, including multiple system atrophy (MSA); and TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). PSP and CBD show characteristic tau-positive astrocytic inclusions known as tufted astrocytes and astrocytic plaques, respectively. PiD shows tau-positive neuronal inclusions termed Pick bodies. MSA is characterized by α-synuclein-positive oligodendroglial inclusions, called glial cytoplasmic inclusions. ALS- and FTLD-TDP show TDP-43-positive neuronal inclusions, such as skein-like and round inclusions. Huntington's disease shows polyglutamine-positive neuronal inclusions, and Creutzfeldt-Jakob disease shows diffuse deposition of granular prions in the neuropil. The atypical proteins in these diseases have abnormal conformational properties. A comprehensive comparison of the clinical findings and neuropathological observations, including neuroanatomy and images acquired during life, is important to improve the sensitivity of clinical diagnosis.

Atypical Structure of Broca's Area in a Patient with Primary Progressive Atrophy Syndrome at the Onset of Alzheimer's Disease

This article presents a clinical case of Alzheimer’s disease with a debut as primary progressive aphasia syndrome. Insufficient use of routine magnetic resonance imaging in this case in the diagnosis of neurodegenerative diseases and the advantage of such additional neuroimaging methods as positron emission tomography, functional magnetic resonance imaging with a scale assessment of atrophic changes. Additional neuroimaging techniques have been shown to significantly improve the early detection of pathological changes in brain structures and to reveal the location of functional areas involved in the neurodegenerative process.

CPD: Artificial intelligence 3

Australia-based researchers and academics, Md Mahmudul Hasan, Jack Phu, Arcot Sowmya, Erik Meijering and Michael Kalloniatis continue our series on AI and eye care with a summary of evidence highlighting the role AI could play in glaucoma and neurodegenerative disease diagnosis

Clinical Arterial Spin-Labeling MR Imaging to Screen for Typical and Atypical Neurodegenerative Disease in the New Era of Alzheimer Treatment.

The clinical standard of care in the diagnosis of neurodegenerative diseases relies on [18F] FDG-PET/CT or PET MR imaging. Limitations of FDG-PET include cost, the need for IV access, radiation exposure, and availability. Arterial spin-labeling MR imaging has been shown in research settings to be useful as a proxy for FDG-PET in differentiating Alzheimer disease from frontotemporal dementia. However, it is not yet widely used in clinical practice, except in cerebrovascular disease. Here, we present 7 patients, imaged with our routine clinical protocol with diverse presentations of Alzheimer disease and other neurodegenerative diseases, in whom arterial spin-labeling-derived reduced CBF correlated with hypometabolism or amyloid/tau deposition on PET. Our case series illustrates the clinical diagnostic utility of arterial spin-labeling MR imaging as a fast, accessible, and noncontrast screening tool for neurodegenerative disease. Arterial spin-labeling MR imaging can guide patient selection for subsequent PET or fluid biomarker work-up, as well as for possible therapy with antiamyloid monoclonal antibodies.

Reactive antibodies against brain antigens as serological biomarkers of neurodegenerative diseases

The aging of the population, attributed to increased life expectancy, coincides with a rise in the prevalence of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. The symptoms of these disorders, such as motor disturbances and cognitive impairment, occur only after significant neurological damage, greatly diminishing the effectiveness of treatments. Consequently, achieving early diagnosis of neurodegenerative diseases stands as a paramount global health challenge. These conditions are characterized by the progressive loss of specific neuronal groups in the nervous system, resulting in dysfunction and eventual cell death in the brain. Although the exact cause of neuronal degeneration remains largely unknown, recent studies have revealed the significant involvement of the immune system in the pathogenesis of these diseases. Notably, the identification of reactive antibodies targeting specific antigens has highlighted a close association between immune mechanisms and the neurodegenerative process. Thus, the aim of this review is to explore the mechanisms of the adaptive immune system and their impact on the pathogenesis of neurodegenerative diseases, with a particular focus on reactive antibodies and their potential as diagnostic biomarkers.

Clinical presentation and diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: a literature analysis of case studies.

Because adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, rapidly progressive, debilitating, and ultimately fatal neurodegenerative disease, a rapid and accurate diagnosis is critical. This analysis examined the frequency of initial misdiagnosis of ALSP via comprehensive review of peer-reviewed published cases. Data were extracted from a MEDLINE search via PubMed (January 1, 1980, through March 22, 2022) from eligible published case reports/series for patients with an ALSP diagnosis that had been confirmed by testing for the colony-stimulating factor-1 receptor gene (CSF1R) mutation. Patient demographics, clinical symptoms, brain imaging, and initial diagnosis data were summarized descriptively. Categorical data for patient demographics, symptoms, and brain imaging were stratified by initial diagnosis category to test for differences in initial diagnosis based on each variable. Data were extracted from a cohort of 291 patients with ALSP from 93 published case reports and case series. Mean (standard deviation) age of symptom onset was 43.2 (11.6) years. A family history of ALSP was observed in 59.1% of patients. Cognitive impairment (47.1%) and behavioral and psychiatric abnormalities (26.8%) were the most frequently reported initial symptoms. Of 291 total cases, an accurate initial diagnosis of ALSP was made in 72 cases (24.7%) and the most frequent initial misdiagnosis categories were frontotemporal dementia (28 [9.6%]) and multiple sclerosis (21 [7.2%]). Of the 219 cases (75.3%) that were initially mis- or undiagnosed, 206 cases (94.1%) were later confirmed as ALSP by immunohistology, imaging, and/or genetic testing; for the remaining 13 cases, no final diagnosis was reported. Initial diagnosis category varied based on age, family history, geographic region, mode of inheritance, and presenting symptoms of pyramidal or extrapyramidal motor dysfunction, behavioral and psychiatric abnormalities, cognitive impairment, and speech difficulty. Brain imaging abnormalities were common, and initial diagnosis category was significantly associated with white matter hyperintensities, white matter calcifications, and ventricular enlargement. In this literature analysis, ALSP was frequently misdiagnosed. Improving awareness of this condition and distinguishing it from other conditions with overlapping presenting symptoms is important for timely management of a rapidly progressive disease such as ALSP.

Machine Learning and Digital Biomarkers Can Detect Early Stages of Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) are devastating conditions that can develop without noticeable symptoms, causing irreversible damage to neurons before any signs become clinically evident. NDs are a major cause of disability and mortality worldwide. Currently, there are no cures or treatments to halt their progression. Therefore, the development of early detection methods is urgently needed to delay neuronal loss as soon as possible. Despite advancements in Medtech, the early diagnosis of NDs remains a challenge at the intersection of medical, IT, and regulatory fields. Thus, this review explores "digital biomarkers" (tools designed for remote neurocognitive data collection and AI analysis) as a potential solution. The review summarizes that recent studies combining AI with digital biomarkers suggest the possibility of identifying pre-symptomatic indicators of NDs. For instance, research utilizing convolutional neural networks for eye tracking has achieved significant diagnostic accuracies. ROC-AUC scores reached up to 0.88, indicating high model performance in differentiating between PD patients and healthy controls. Similarly, advancements in facial expression analysis through tools have demonstrated significant potential in detecting emotional changes in ND patients, with some models reaching an accuracy of 0.89 and a precision of 0.85. This review follows a structured approach to article selection, starting with a comprehensive database search and culminating in a rigorous quality assessment and meaning for NDs of the different methods. The process is visualized in 10 tables with 54 parameters describing different approaches and their consequences for understanding various mechanisms in ND changes. However, these methods also face challenges related to data accuracy and privacy concerns. To address these issues, this review proposes strategies that emphasize the need for rigorous validation and rapid integration into clinical practice. Such integration could transform ND diagnostics, making early detection tools more cost-effective and globally accessible. In conclusion, this review underscores the urgent need to incorporate validated digital health tools into mainstream medical practice. This integration could indicate a new era in the early diagnosis of neurodegenerative diseases, potentially altering the trajectory of these conditions for millions worldwide. Thus, by highlighting specific and statistically significant findings, this review demonstrates the current progress in this field and the potential impact of these advancements on the global management of NDs.

Brain pathology and symptoms linked to concussion history: beyond chronic traumatic encephalopathy.

Repeated head trauma acquired through sports injuries has been associated with the development of long-term disabling symptoms that negatively impact the quality of life. In this retrospective case series, 52 male former professional athletes involved in contact sports and with a history of multiple concussions were evaluated for chronic clinical symptoms and post-mortem neuropathological diagnoses. The clinical symptoms of 19 cases were examined in greater detail for symptom type, severity and duration. Information on neurological, psychiatric and physical symptoms, substance use profiles and concussion histories was obtained from the athletes' next of kin and assessed in relation to post-mortem neuropathological diagnoses. Cases were categorized into three different neuropathological groups: no major neuropathological findings, the presence of only chronic traumatic encephalopathy (CTE) and the diagnosis(es) of other neurodegenerative diseases. Age at death and the presence of DNA damage in the post-mortem brains were analysed for correlation with the clinical symptoms. In this case series, 14/52 (26.9%) cases (mean age 48.2 ± 11.4) had neuropathological evidence of low-stage/low-burden CTE. A total of 11/52 (21.2%) cases (mean age 38.7 ± 12.7) presented a similar profile and severity of behavioural symptoms to those with CTE, despite the lack of significant post-mortem neuropathological findings. A total of 27/52 (51.9%) cases (mean age 75.5 ± 8.7) presented with complex post-mortem neurodegenerative diagnoses, including Alzheimer's disease and other mixed pathologies, and clinical symptoms associated with language, memory and sensory dysfunction. The presence of DNA damage in the brain was found in all neuropathological groups, predominantly in the ependymal lining of ventricles, and phosphorylated histone H2AX staining was correlated with higher age at death (r = 0.59) and symptoms of language dysfunction (r = 0.56). Findings from our case series suggest that post-concussive symptoms are not driven by CTE. Our findings show that proteinopathies alone may not account for the complexity of the clinical manifestations and suggest the possibility of other drivers, such as DNA damage, as potentially useful markers of brain trauma. Broadening the search for biological markers that reflect the effects of brain injury, even when proteinopathy is not observed, and taking a symptom-driven approach are therefore advised.

Early Diagnosis of Neurodegenerative Diseases: What Has Been Undertaken to Promote the Transition from PET to Fluorescence Tracers.

Alzheimer's Disease (AD) and Parkinson's Disease (PD) represent two among the most frequent neurodegenerative diseases worldwide. A common hallmark of these pathologies is the misfolding and consequent aggregation of amyloid proteins into soluble oligomers and insoluble β-sheet-rich fibrils, which ultimately lead to neurotoxicity and cell death. After a hundred years of research on the subject, this is the only reliable histopathological feature in our hands. Since AD and PD are diagnosed only once neuronal death and the first symptoms have appeared, the early detection of these diseases is currently impossible. At present, there is no effective drug available, and patients are left with symptomatic and inconclusive therapies. Several reasons could be associated with the lack of effective therapeutic treatments. One of the most important factors is the lack of selective probes capable of detecting, as early as possible, the most toxic amyloid species involved in the onset of these pathologies. In this regard, chemical probes able to detect and distinguish among different amyloid aggregates are urgently needed. In this article, we will review and put into perspective results from ex vivo and in vivo studies performed on compounds specifically interacting with such early species. Following a general overview on the three different amyloid proteins leading to insoluble β-sheet-rich amyloid deposits (amyloid β1-42 peptide, Tau, and α-synuclein), a list of the advantages and disadvantages of the approaches employed to date is discussed, with particular attention paid to the translation of fluorescence imaging into clinical applications. Furthermore, we also discuss how the progress achieved in detecting the amyloids of one neurodegenerative disease could be leveraged for research into another amyloidosis. As evidenced by a critical analysis of the state of the art, substantial work still needs to be conducted. Indeed, the early diagnosis of neurodegenerative diseases is a priority, and we believe that this review could be a useful tool for better investigating this field.

Applications of Raman spectroscopy in the diagnosis and monitoring of neurodegenerative diseases.

Raman scattering is an inelastic light scattering that occurs in a manner reflective of the molecular vibrations of molecular structures and chemical conditions in a given sample of interest. Energy changes in the scattered light can be assessed to determine the vibration mode and associated molecular and chemical conditions within the sample, providing a molecular fingerprint suitable for sample identification and characterization. Raman spectroscopy represents a particularly promising approach to the molecular analysis of many diseases owing to clinical advantages including its instantaneous nature and associated high degree of stability, as well as its ability to yield signal outputs corresponding to a single molecule type without any interference from other molecules as a result of its narrow peak width. This technology is thus ideally suited to the simultaneous assessment of multiple analytes. Neurodegenerative diseases represent an increasingly significant threat to global public health owing to progressive population aging, imposing a severe physical and social burden on affected patients who tend to develop cognitive and/or motor deficits beginning between the ages of 50 and 70. Owing to a relatively limited understanding of the etiological basis for these diseases, treatments are lacking for the most common neurodegenerative diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The present review was formulated with the goal of briefly explaining the principle of Raman spectroscopy and discussing its potential applications in the diagnosis and evaluation of neurodegenerative diseases, with a particular emphasis on the research prospects of this novel technological platform.

O-GlcNAcylation and Its Roles in Neurodegenerative Diseases.

As a non-classical post-translational modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is widely found in human organ systems, particularly in our brains, and is indispensable for healthy cell biology. With the increasing age of the global population, the incidence of neurodegenerative diseases is increasing, too. The common characteristic of these disorders is the aggregation of abnormal proteins in the brain. Current research has found that O-GlcNAcylation dysregulation is involved in misfolding or aggregation of these abnormal proteins to mediate disease progression, but the specific mechanism has not been defined. This paper reviews recent studies on O-GlcNAcylation's roles in several neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Machado-Joseph's disease, and giant axonal neuropathy, and shows that O-GlcNAcylation, as glucose metabolism sensor, mediating synaptic function, participating in oxidative stress response and signaling pathway conduction, directly or indirectly regulates characteristic pathological protein toxicity and affects disease progression. The existing results suggest that targeting O-GlcNAcylation will provide new ideas for clinical diagnosis, prevention, and treatment of neurodegenerative diseases.

Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings.

We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegenerationbiomarkermeasurements from venous dried plasma spots (DPSv enous) for the diagnosis and monitoring of neurodegenerative diseases in remote settings. In a discovery (n=154) and a validation cohort (n=115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p-tau181 and p-tau217) were measured in paired DPSvenous and ethylenediaminetetraacetic acid plasma samples with single-molecule array. In the validation cohort, a subset of participants (n=99) had cerebrospinal fluid (CSF) biomarkers. All DPSvenous and plasma analytes correlated significantly, except for Aβ42. In the validation cohort, DPSvenous GFAP, NfL, p-tau181, and p-tau217 differed between CSF Aβ-positive and -negative individuals and were associated with worsening cognition. Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPSvenous extends the utility of blood-based biomarkers to remote settings with simplified sampling conditions, storage, and logistics. A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegenerationwere detectable in dried plasma spots (DPSvenous). DPSvenous biomarkers correlated with standard procedures and cognitive status. DPSvenous biomarkers had a good diagnostic accuracy discriminating amyloid status. Our findings show the potential interchangeability of DPSvenous and plasmasampling. DPSvenous may facilitate remote and temperature-independent sampling for AD biomarker measurement. Innovative tools for blood biomarker sampling may help recognizing the earliest changes of AD.

Retinal OCT biomarkers and neurodegenerative diseases of the central nervous system beyond Alzheimer's disease

Optical coherence tomography (OCT) biomarkers are increasingly used by neurologists, psychiatrists, and ophthalmologists for the diagnosis, prognosis, and follow-up of neurodegenerative diseases. Long-term data on OCT biomarkers of selected primary and secondary neurodegenerative diseases of the central nervous system (CNS), such as multiple sclerosis (MS) or Parkinson's disease, are already available in part. In addition, there are rare neurodegenerative diseases with early disease onset that may show OCT abnormalities. Aliterature review on the association of OCT biomarkers with neurodegenerative diseases of the CNS beyond Alzheimer's disease is presented. Parkinson's disease, MS, Friedreich's ataxia, Huntington's disease, spinocerebellar ataxia, and lysosomal storage diseases are addressed. Relevant OCT biomarkers of neurodegenerative diseases are the macular ganglion cell inner plexiform layer (GCIPL) and the peripapillary retinal nerve fiber layer (pRNFL) thickness. Different sectors may be affected depending on the disease entity in addition to global pRFNL reduction. OCT‑angiography (OCT-A) is also increasingly used as abiomarker in neurodegenerative diseases. Optical coherence tomography biomarkers are used in an interdisciplinary context. Retinal pathologies should be excluded by an ophthalmologist. While OCT biomarkers are increasingly used clinically in MS, the benefit in other neurodegenerative diseases, especially the rare ones, is less well documented. Further longitudinal studies are required.

Potential roles of telomeres and telomerase in neurodegenerative diseases

Telomeres, essential DNA-protein complexes located at chromosome ends, play a critical role in preventing chromosome fusion, recombination, and degradation, thus ensuring genomic stability. When telomeres reach a limiting shortened length, they will activate DNA damage checkpoints, stop cell division and trigger replicative senescence. Telomerase is composed of RNA and protein, which can synthesize telomeres repeat sequences, and elongate telomeres. Studies have shown that telomere length (TL) and telomerase activity are closely involved in aging, aging-related degenerative diseases, and tumors. Neurodegenerative diseases (NDDs) are one of the major aging-related diseases caused by both genetic and environmental factors, characterized by insidious onset, difficult diagnosis, irreversible disease progression, and lack of effective treatments, which brings a heavy burden to society and families. Currently, many studies have noted variations in leukocyte telomere length (LTL) and telomerase activity in NDDs, suggesting a vital role for telomeres and telomerase in NDD pathogenesis. This review explores the relationship between TL and NDDs, examines telomerase as a potential therapeutic target, and discusses emerging biomarkers and intervention strategies for NDD diagnosis and treatment.