scholarly journals Contributions of Molecular and Optical Techniques to the Clinical Diagnosis of Alzheimer’s Disease

2020 ◽  
Vol 10 (11) ◽  
pp. 815
Author(s):  
Edoardo Bistaffa ◽  
Fabrizio Tagliavini ◽  
Paolo Matteini ◽  
Fabio Moda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Diagnosis ◽  
Neurodegenerative Disorder ◽  
Phenotypic Variability ◽  
Surface Enhanced Raman Spectroscopy ◽  
Reaction Products ◽  
Surface Enhanced Raman ◽  
Amyloid Aβ ◽  
Folded Proteins

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. The distinctive neuropathological feature of AD is the intracerebral accumulation of two abnormally folded proteins: β-amyloid (Aβ) in the form of extracellular plaques, and tau in the form of intracellular neurofibrillary tangles. These proteins are considered disease-specific biomarkers, and the definite diagnosis of AD relies on their post-mortem identification in the brain. The clinical diagnosis of AD is challenging, especially in the early stages. The disease is highly heterogeneous in terms of clinical presentation and neuropathological features. This phenotypic variability seems to be partially due to the presence of distinct Aβ conformers, referred to as strains. With the development of an innovative technique named Real-Time Quaking-Induced Conversion (RT-QuIC), traces of Aβ strains were found in the cerebrospinal fluid of AD patients. Emerging evidence suggests that different conformers may transmit their strain signature to the RT-QuIC reaction products. In this review, we describe the current challenges for the clinical diagnosis of AD and describe how the RT-QuIC products could be analyzed by a surface-enhanced Raman spectroscopy (SERS)-based systems to reveal the presence of strain signatures, eventually leading to early diagnosis of AD with the recognition of individual disease phenotype.

scholarly journals Autophagy in Alzheimer’s disease pathogenesis: therapeutic potential and future perspectives

2020 ◽  
Author(s):  
Zhigang Zhang ◽  
You-Qiang Song ◽  
Jie Tu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
The Elderly ◽  
Future Perspectives ◽  
Aβ Peptides ◽  
Evolutionarily Conserved ◽  
Amyloid Aβ ◽  
Folded Proteins

Alzheimer’s disease (AD) is a complex neurodegenerative disease in the elderly. It is the most common cause of dementia in human. AD is characterized by accumulation of abnormal protein aggregates including amyloid plaques (composed of beta-amyloid (Aβ) peptides) and neurofibrillary tangles (formed by hyper-phosphorylated tau protein). Besides, synaptic plasticity, neuroinflammation, calcium signaling etc. are found to be dysfunctional as well in AD patients. Autophagy is an evolutionarily conserved lysosome-dependent cellular event in eukaryotes. It is closely linked to the modulation of protein metabolism, through which damaged organelles and mis-folded proteins are degraded and then recycled to maintain protein homeostasis. Accumulating evidence has showed that impaired autophagy contributes to AD pathogenesis. In the present review, we highlight the role of autophagy, including bulk and selective autophagy, in regulating metabolic circuits in AD pathogenesis. We also discuss the potential and future perspectives of autophagy-inducing strategy in AD therapeutics.

scholarly journals Alzheimer’s disease: new concepts on the role of autoimmunity and of NLRP3 inflammasome in the pathogenesis of the disease

2020 ◽  
Vol 18 ◽  
Author(s):  
Cinzia Severini ◽  
Christian Barbato ◽  
Maria Grazia Di Certo ◽  
Francesca Gabanella ◽  
Carla Petrella ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Critical Factor ◽  
Innate Immune Responses ◽  
New Concepts ◽  
Amyloid Aβ

: Alzheimer’s disease (AD), recognized as the most common neurodegenerative disorder, is clinically characterized by the presence of extracellular beta amyloid (Aβ) plaques and by intracellular neurofibrillary tau tangles, accompanied by glial activation and neuroinflammation. Increasing evidence suggests that self-misfolded proteins stimulate an immune response mediated by glial cells, inducing release of inflammatory mediators and the recruitment of peripheral macrophages into the brain, which in turn aggravate AD pathology. Aim of the present review is to update the current knowledge on the role of autoimmunity and neuroinflammation in the pathogenesis of the disease, indicating new target for therapeutic intervention. We mainly focused on the NLRP3 microglial inflammasome as a critical factor in stimulating innate immune responses, thus sustaining chronic inflammation. Additionally, we discussed the involvement of the NLRP3 inflammasome in the gut-brain axis. Direct targeting the NLRP3 inflammasome and the associated receptors could be a potential pharmacological strategy, since its inhibition would selectively reduce AD neuroinflammation.

scholarly journals Application of CRISPR/Cas9 in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Likui Lu ◽  
Xi Yu ◽  
Yongle Cai ◽  
Miao Sun ◽  
Hao Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Complex Disease ◽  
Neurodegenerative Disorder ◽  
Target Therapy ◽  
Abnormal Behavior ◽  
Psychological Suffering ◽  
Pathogenic Genes ◽  
Hyperphosphorylated Tau Protein ◽  
Amyloid Aβ

Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder clinically characterized by cognitive impairment, abnormal behavior, and social deficits, which is intimately linked with excessive β-amyloid (Aβ) protein deposition along with many other misfolded proteins, neurofibrillary tangles formed by hyperphosphorylated tau protein aggregates, and mitochondrial damage in neurons, leading to neuron loss. Currently, research on the pathological mechanism of AD has been elucidated for decades, still no effective treatment for this complex disease was developed, and the existing therapeutic strategies are extremely erratic, thereby leading to irreversible and progressive cognitive decline in AD patients. Due to gradually mental dyscapacitating of AD patients, AD not only brings serious physical and psychological suffering to patients themselves, but also imposes huge economic burdens on family and society. Accordingly, it is very imperative to recapitulate the progress of gene editing-based precision medicine in the emerging fields. In this review, we will mainly focus on the application of CRISPR/Cas9 technique in the fields of AD research and gene therapy, and summarize the application of CRISPR/Cas9 in the aspects of AD model construction, screening of pathogenic genes, and target therapy. Finally, the development of delivery systems, which is a major challenge that hinders the clinical application of CRISPR/Cas9 technology will also be discussed.

PLGA-Based Curcumin Delivery System: An Interesting Therapeutic Approach in Treatment of Alzheimer’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Sanaz Keshavarz Shahbaz ◽  
Khadijeh Koushki ◽  
Thozhukat Sathyapalan ◽  
Muhammed Majeed ◽  
Amirhossein Sahebkar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Disorders ◽  
Neurodegenerative Disorder ◽  
Aqueous Solubility ◽  
Plga Nanoparticles ◽  
Progressive Degeneration ◽  
Hyperphosphorylated Tau Protein ◽  
Amyloid Aβ ◽  
Β Amyloid

: Progressive degeneration and dysfunction of the nervous system because of oxidative stress, aggregations of misfolded proteins, and neuroinflammation are the key pathological features of neurodegenerative diseases. Alzheimer's disease is a chronic neurodegenerative disorder driven by uncontrolled extracellular deposition of β-amyloid (Aβ) in the amyloid plaques and intracellular accumulation of hyperphosphorylated tau protein. Curcumin is a hydrophobic polyphenol with noticeable neuroprotective and anti-inflammatory effects that can cross the blood-brain barrier. Therefore, it is widely studied for the alleviation of inflammatory and neurological disorders. However, the clinical application of curcumin is limited due to its low aqueous solubility and bioavailability. Recently, nano-based curcumin delivery systems are developed to overcome these limitations effectively. This review article discusses the effects and potential mechanisms of curcumin-loaded PLGA nanoparticles in Alzheimer’s disease.

Receptor-Interacting Protein Kinase 1 (RIPK1) as a Potential Therapeutic Target: An Overview of Its Possible Role in the Pathogenesis of Alzheimer's Disease

2019 ◽  
Vol 16 (10) ◽  
pp. 907-918
Author(s):  
Hong Hao Chan ◽  
Rhun Yian Koh ◽  
Chooi Ling Lim ◽  
Chee Onn Leong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Kinase ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Current Treatment ◽  
Interacting Protein ◽  
Amyloid Aβ ◽  
Cognition Impairment ◽  
Insight Into

Alzheimer’s Disease (AD) is an age-dependent neurodegenerative disorder, the most common type of dementia that is clinically characterized by the presence of beta-amyloid (Aβ) extracellularly and intraneuronal tau protein tangles that eventually leads to the onset of memory and cognition impairment, development of psychiatric symptoms and behavioral disorders that affect basic daily activities. Current treatment approved by the U.S Food and Drug Administration (FDA) for AD is mainly focused on the symptoms but not on the pathogenesis of the disease. Recently, receptor-interacting protein kinase 1 (RIPK1) has been identified as a key component in the pathogenesis of AD through necroptosis. Furthermore, genetic and pharmacological suppression of RIPK1 has been shown to revert the phenotype of AD and its mediating pathway is yet to be deciphered. This review is aimed to provide an overview of the pathogenesis and current treatment of AD with the involvement of autophagy as well as providing a novel insight into RIPK1 in reverting the progression of AD, probably through an autophagy machinery.

scholarly journals Multivariate Statistical Analysis of Surface Enhanced Raman Spectra of Human Serum for Alzheimer’s Disease Diagnosis

2019 ◽  
Vol 9 (16) ◽  
pp. 3256 ◽  
Author(s):  
Elena Ryzhikova ◽  
Nicole M. Ralbovsky ◽  
Lenka Halámková ◽  
Dzintra Celmins ◽  
Paula Malone ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Statistical Analysis ◽  
Blood Serum ◽  
Multivariate Statistical Analysis ◽  
Disease Diagnosis ◽  
Surface Enhanced Raman Spectroscopy ◽  
Multivariate Statistical ◽  
Surface Enhanced ◽  
Surface Enhanced Raman

Alzheimer’s disease (AD) is the most common form of dementia worldwide and is characterized by progressive cognitive decline. Along with being incurable and lethal, AD is difficult to diagnose with high levels of accuracy. Blood serum from Alzheimer’s disease (AD) patients was analyzed by surface-enhanced Raman spectroscopy (SERS) coupled with multivariate statistical analysis. The obtained spectra were compared with spectra from healthy controls (HC) to develop a simple test for AD detection. Serum spectra from AD patients were further compared to spectra from patients with other neurodegenerative dementias (OD). Colloidal silver nanoparticles (AgNPs) were used as the SERS-active substrates. Classification experiments involving serum SERS spectra using artificial neural networks (ANNs) achieved a diagnostic sensitivity around 96% for differentiating AD samples from HC samples in a binary model and 98% for differentiating AD, HC, and OD samples in a tertiary model. The results from this proof-of-concept study demonstrate the great potential of SERS blood serum analysis to be developed further into a novel clinical assay for the effective and accurate diagnosis of AD.

scholarly journals Molecular Mechanism of Autophagy: Its Role in the Therapy of Alzheimer’s Disease

2020 ◽  
Vol 18 (8) ◽  
pp. 720-739 ◽  
Author(s):  
Yuan Zhao ◽  
Yidan Zhang ◽  
Jian Zhang ◽  
Xiangjian Zhang ◽  
Guofeng Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Protein Quality ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Neuritic Plaques ◽  
Progressive Dementia ◽  
Disease Modifying Therapies ◽  
Amyloid Aβ

: Alzheimer’s disease (AD) is a neurodegenerative disorder of progressive dementia that is characterized by the accumulation of beta-amyloid (Aβ)-containing neuritic plaques and intracellular Tau protein tangles. This distinctive pathology indicates that the protein quality control is compromised in AD. Autophagy functions as a “neuronal housekeeper” that eliminates aberrant protein aggregates by wrapping then into autophagosomes and delivering them to lysosomes for degradation. Several studies have suggested that autophagy deficits in autophagy participate in the accumulation and propagation of misfolded proteins (including Aβ and Tau). In this review, we summarize current knowledge of autophagy in the pathogenesis of AD, as well as some pathways targeting the restoration of autophagy. Moreover, we discuss how these aspects can contribute to the development of disease-modifying therapies in AD.

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.

Picture Recognition Errors in the Differential Diagnosis of Alzheimer’s Disease

2019 ◽  
Vol 30 (3) ◽  
pp. 157-168
Author(s):  
Helmut Hildebrandt ◽  
Jana Schill ◽  
Jana Bördgen ◽  
Andreas Kastrup ◽  
Paul Eling
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Clinical Diagnosis ◽  
Response Bias ◽  
Recognition Task ◽  
Discriminatory Power ◽  
False Alarms ◽  
Picture Recognition ◽  
Recognition Errors

Abstract. This article explores the possibility of differentiating between patients suffering from Alzheimer’s disease (AD) and patients with other kinds of dementia by focusing on false alarms (FAs) on a picture recognition task (PRT). In Study 1, we compared AD and non-AD patients on the PRT and found that FAs discriminate well between these groups. Study 2 served to improve the discriminatory power of the FA score on the picture recognition task by adding associated pairs. Here, too, the FA score differentiated well between AD and non-AD patients, though the discriminatory power did not improve. The findings suggest that AD patients show a liberal response bias. Taken together, these studies suggest that FAs in picture recognition are of major importance for the clinical diagnosis of AD.

Sign in / Sign up

Export Citation Format

Share Document