scholarly journals A combined miRNA–piRNA signature to detect Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gaurav Jain ◽  
Anne Stuendl ◽  
Pooja Rao ◽  
Tea Berulava ◽  
Tonatiuh Pena Centeno ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Noncoding Rna ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Replication Cohort ◽  
Small Noncoding Rna ◽  
Human Cerebrospinal Fluid ◽  
Generation Sequencing ◽  
Common Neurodegenerative Disorder

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild–cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.

scholarly journals Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

2020 ◽  
Vol 21 (16) ◽  
pp. 5858 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Md. Tanvir Kabir ◽  
Md. Sohanur Rahman ◽  
Tapan Behl ◽  
Philippe Jeandet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Amyloid Β ◽  
Aβ Oligomers ◽  
Aβ Aggregation ◽  
Clinical Benefits

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-β (Aβ), a peptide of 40–42 amino acids. The conversion of Aβ into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aβ accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aβ monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aβ and antagonize Aβ aggregation, or raise Aβ clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aβ which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aβ oligomers have exhibited exciting findings. Nevertheless, Aβ oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aβ monomer or Aβ plaques ought to have displayed valuable clinical benefits. In this article, Aβ-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

scholarly journals Endosomal Trafficking in Alzheimer's Disease, Parkinson's Disease, and Neuronal Ceroid Lipofuscinosis

2020 ◽  
Vol 40 (19) ◽  
Author(s):  
Yasir H. Qureshi ◽  
Penelope Baez ◽  
Christiane Reitz
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Endosomal Trafficking ◽  
Lysosomal Storage ◽  
Ceroid Lipofuscinosis ◽  
Common Neurodegenerative Disorder

ABSTRACT Neuronal ceroid lipofuscinosis (NCL) is one of the most prevalent neurodegenerative disorders of early life, Parkinson’s disease (PD) is the most common neurodegenerative disorder of midlife, while Alzheimer’s disease (AD) is the most common neurodegenerative disorder of late life. While they are phenotypically distinct, recent studies suggest that they share a biological pathway, retromer-dependent endosomal trafficking. A retromer is a multimodular protein assembly critical for sorting and trafficking cargo out of the endosome. As a lysosomal storage disease, all 13 of NCL’s causative genes affect endolysosomal function, and at least four have been directly linked to retromer. PD has several known causative genes, with one directly linked to retromer and others causing endolysosomal dysfunction. AD has over 25 causative genes/risk factors, with several of them linked to retromer or endosomal trafficking dysfunction. In this article, we summarize the emerging evidence on the association of genes causing NCL with retromer function and endosomal trafficking, review the recent evidence linking NCL genes to AD, and discuss how NCL, AD, and PD converge on a shared molecular pathway. We also discuss this pathway’s role in microglia and neurons, cell populations which are critical to proper brain homeostasis and whose dysfunction plays a key role in neurodegeneration.

scholarly journals Topological Dissection of Proteomic Changes Linked to the Limbic Stage of Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Erika Velásquez ◽  
Beáta Szeitz ◽  
Jeovanis Gil ◽  
Jimmy Rodriguez ◽  
Miklós Palkovits ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Brain Area ◽  
Disease Classification ◽  
Molecular Heterogeneity ◽  
Braak Stage ◽  
Tissue Samples ◽  
Major Player

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. In AD, neurodegeneration spreads throughout different areas of the central nervous system (CNS) in a gradual and predictable pattern, causing progressive memory decline and cognitive impairment. Deposition of neurofibrillary tangles (NFTs) in specific CNS regions correlates with the severity of AD and constitutes the basis for disease classification into different Braak stages (I-VI). Early clinical symptoms are typically associated with stages III-IV (i.e., limbic stages) when the involvement of the hippocampus begins. Histopathological changes in AD have been linked to brain proteome alterations, including aberrant posttranslational modifications (PTMs) such as the hyperphosphorylation of Tau. Most proteomic studies to date have focused on AD progression across different stages of the disease, by targeting one specific brain area at a time. However, in AD vulnerable regions, stage-specific proteomic alterations, including changes in PTM status occur in parallel and remain poorly characterized. Here, we conducted proteomic, phosphoproteomic, and acetylomic analyses of human postmortem tissue samples from AD (Braak stage III-IV, n=11) and control brains (n=12), covering all anatomical areas affected during the limbic stage of the disease (total hippocampus, CA1, entorhinal and perirhinal cortices). Overall, ~6000 proteins, ~9000 unique phosphopeptides and 221 acetylated peptides were accurately quantified across all tissues. Our results reveal significant proteome changes in AD brains compared to controls. Among others, we have observed the dysregulation of pathways related to the adaptive and innate immune responses, including several altered antimicrobial peptides (AMPs). Notably, some of these changes were restricted to specific anatomical areas, while others altered according to disease progression across the regions studied. Our data highlights the molecular heterogeneity of AD and the relevance of neuroinflammation as a major player in AD pathology. Data are available via ProteomeXchange with identifier PXD027173.

The Investigation of Simultaneous EEG and Eye Tracking Characteristics During Fixation Task in Mild Alzheimer’s Disease

2020 ◽  
pp. 155005942093275
Author(s):  
Malihe Moghadami ◽  
Sahar Moghimi ◽  
Ali Moghimi ◽  
Gholam Reza Malekzadeh ◽  
Javad Salehi Fadardi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Eye Tracking ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Alpha Power ◽  
Fixational Eye Movements ◽  
Fixation Task ◽  
Fixation Frequency

Alzheimer’s disease (AD) is a neurodegenerative disorder that occurs many years before the first clinical symptoms. Finding more exact, significant, and valuable criteria or indices for the diagnosis of the mild form of Alzheimer’s disease is very important for clinical and research purposes. Electroencephalography (EEG) and eye tracking biomarkers would provide noninvasive tools for the early detection of AD. Due to the advantages of EEG and eye tracking, in this study, we employed them simultaneously to conduct research on the mild AD. For this purpose, 19 patients with mild AD were compared with 19 gender- and age-matched normal subjects who did not have any history of cognitive or neurological disorders. EEG and eye-tracking data were concurrently collected in both groups in a fixation task. Our results revealed that the total fixation duration was significantly shorter for the AD patients, but their fixation frequency was more than that of the controls. In addition, increased theta power and decreased alpha power were observed in the AD group. Interestingly, there was a statistically significant correlation between fixation frequency and alpha power in the parietal area in the control group. However, this connection was not statistically significant in the AD group. The findings also indicated an elevated coherence in the AD patients in the parieto-occipital area. It is assumed that the AD patients might use the neural compensational processes for the fixation state. This study provides evidence for the simultaneously EEG and eye-tracking changes in the areas, which are involved in the control of the fixational eye movements.

scholarly journals Non-motor Symptoms in Parkinson’s Disease

2009 ◽  
Vol 4 (1) ◽  
pp. 25 ◽  
Author(s):  
Angelo Antonini ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Motor Symptoms ◽  
Significant Morbidity ◽  
Non Motor Symptoms ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and is responsible for significant morbidity and costs. Non-motor manifestations of PD can be as disabling as the classic motor symptoms. Moreover, medications used to treat PD motor symptoms may have variable effects on these non-motor domains.

scholarly journals The fluid biomarkers of Alzheimer’s disease

2021 ◽  
Vol 7 (1) ◽  
pp. 1-16
Author(s):  
Qinyu Peng ◽  
Zhentao Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Disorder ◽  
Future Prospects ◽  
Research Directions ◽  
Disease Modifying Therapies ◽  
Highly Sensitive ◽  
Disease Modifying ◽  
Common Neurodegenerative Disorder

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. However, it still has no available disease‐modifying therapies. Its pathology cascade begins decades before symptomatic presentation. For these reasons, highly sensitive and highly specific fluid biomarkers should be developed for the early diagnosis of AD. In this study, the well‐established and emerging fluid biomarkers of AD are summarized, and recent advances on their role in early diagnosis and progression monitoring as well as their correlations with AD pathology are highlighted. Future prospects and related research directions are also discussed.

scholarly journals Dysfunction of Synaptic Vesicle Endocytosis in Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Li Zou ◽  
Ye Tian ◽  
Zhentao Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Synaptic Vesicle ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Progressive Disorder ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. It is a chronic and progressive disorder estimated to affect at least 4 million people worldwide. Although the etiology of PD remains unclear, it has been found that the dysfunction of synaptic vesicle endocytosis (SVE) in neural terminal happens before the loss of dopaminergic neurons. Recently, accumulating evidence reveals that the PD-linked synaptic genes, including DNAJC6, SYNJ1, and SH3GL2, significantly contribute to the disruptions of SVE, which is vital for the pathogenesis of PD. In addition, the proteins encoded by other PD-associated genes such as SNCA, LRRK2, PRKN, and DJ-1 also play key roles in the regulation of SVE. Here we present the facts about SVE-related genes and discussed their potential relevance to the pathogenesis of PD.

THE TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS-2 (TREM-2) AS EXPRESSION OF THE RELATIONSHIP BETWEEN MICROGLIA AND ALZHEIMER’S DISEASE: A NOVEL MARKER FOR A PROMISING PATHWAY TO EXPLORE

2018 ◽  
pp. 1-3
Author(s):  
C. Gussago ◽  
M. Casati ◽  
E. Ferri ◽  
B. Arosio
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Myeloid Cells ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell ◽  
The Relationship ◽  
Common Neurodegenerative Disorder

Alzheimer’s disease (AD) is a common neurodegenerative disorder, strongly related with age. It has been reported that genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2), a cell-surface receptor expressed in microglial cells, greatly increase the risk of AD, thus suggesting an involvement of the microglia in the AD pathogenesis. The aim of this report is to provide an overview of the TREM2 and of its possible implication in the pathogenesis of AD.

Connecting Mind-Body Therapy-Mediated Effects to Pathological Features of Alzheimer’s Disease

2020 ◽  
pp. 1-26
Author(s):  
Melanie Hüttenrauch ◽  
José Sócrates Lopez-Noguerola ◽  
Susana Castro-Obregón
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Positive Impact ◽  
Neuropsychiatric Symptoms ◽  
Alternative Interventions ◽  
Positive Effects ◽  
Dementia Patients

Alzheimer’s disease (AD) is a complex, multifactorial neurodegenerative disorder that represents a major and increasing global health challenge. In most cases, the first clinical symptoms of AD are preceded by neuropathological changes in the brain that develop years to decades before their onset. Therefore, research in the last years has focused on this preclinical stage of AD trying to discover intervention strategies that might, if implemented effectively, delay or prevent disease progression. Among those strategies, mind-body therapies such as yoga and meditation have gained increasing interest as complementary alternative interventions. Several studies have reported a positive impact of yoga and meditation on brain health in both healthy older adults and dementia patients. However, the underlying neurobiological mechanisms contributing to these effects are currently not known in detail. More specifically, it is not known whether yogic interventions, directly or indirectly, can modulate risk factors or pathological mechanisms involved in the development of dementia. In this article, we first review the literature on the effects of yogic practices on outcomes such as cognitive functioning and neuropsychiatric symptoms in patients with mild cognitive impairment and dementia. Then, we analyze how yogic interventions affect different risk factors as well as aspects of AD pathophysiology based on observations of studies in healthy individuals or subjects with other conditions than dementia. Finally, we integrate this evidence and propose possible mechanisms that might explain the positive effects of yogic interventions in cognitively impaired individuals.

Auditory Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Care Setting ◽  
Neurodegenerative Disorder ◽  
Disease Process ◽  
Clinical Protocols ◽  
Speech Language Pathologist ◽  
Auditory Dysfunction

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.

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