New approaches for Alzheimer early detection

Background: Alzheimer’s disease (AD) is neurodegenerative and complex, characterized by the progressive loss of neurons, causing cognitive deficits. It’s the leading cause of dementia in the elderly, affecting about 35.6 million people worldwide. The high costs of invasive diagnostic techniques have limited early detection and intervention. Objectives: This review approached some new non-invasive diagnostic techniques involved in AD. Methods: The descriptors used were “Alzheimer’s Disease”, “Biomarkers” and “Early diagnosis”. PubMed database was used during the period of 2016-2021. Articles not related to the proposed theme were excluded, leaving 4 articles. Results: In the last few years, great advances have been made in diagnosing AD, such as brain NMR, CSF biomarkers, Pittsburgh compound B and brain PET scan. Beta-amyloid proteins (βA) and TAU in CSF are the only available markers for AD diagnosis in the clinic. The main limitations are early detection, differential diagnosis and progress disease report. Salivary biomarkers are being studied as a simple non-invasive diagnostic tool, with βA1-42/1-40 and pTAU being the most investigated in AD. Acting as a window on the brain, the retina can reflect the pathogenesis of the brain, with a focus on neurodegeneration and microvascular changes measured using optical coherence tomography technologies. Conclusions: Several criteria have been proposed for the diagnosis of AD, including biomarkers, biological fluids and brain changes detectable by imaging. Early detection of AD is vitally important, as it’ll allow patients to receive adequate and individualized information, care and support.

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When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2018.00038 ◽

2018 ◽

Vol 10 ◽

Cited By ~ 11

Author(s):

Claudio Liguori ◽

Mariangela Pierantozzi ◽

Agostino Chiaravalloti ◽

Giulia M. Sancesario ◽

Nicola B. Mercuri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Late Life ◽

The Elderly ◽

Csf Biomarkers ◽

Late Life Depression

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Natural product-based nanomedicine: Recent advances and issues for the treatment of Alzheimer's disease

Current Neuropharmacology ◽

10.2174/1570159x20666211217163540 ◽

2021 ◽

Vol 20 ◽

Author(s):

Choy Ker Woon ◽

Wong Kah Hui ◽

Razif Abas ◽

Muhammad Huzaimi Haron ◽

Srijit Das ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Natural Products ◽

Medicinal Plants ◽

Drug Transport ◽

The Elderly ◽

Current Evidence ◽

Alternative Approach ◽

Progressive Neurodegeneration ◽

The Brain

: Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and its severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano- sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material’s bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicine-based approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.

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Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease

International Journal of Alzheimer s Disease ◽

10.1155/2018/3128758 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Corona Solana ◽

Raquel Tarazona ◽

Rafael Solana

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nk Cells ◽

Natural Killer ◽

Nk Cell ◽

Neurodegenerative Disorder ◽

The Elderly ◽

Lymphoid Cells ◽

Target Cells ◽

The Brain

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.

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Novel Blood Biomarkers for an Earlier Diagnosis of Alzheimer’s Disease: A Literature Review

International Journal of Medical Students ◽

10.5195/ijms.2020.452 ◽

2020 ◽

Author(s):

Shiavax Rao ◽

Andrew J. Boileau

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Literature Review ◽

Clinical Diagnosis ◽

Sensitivity And Specificity ◽

Memory Loss ◽

High Sensitivity ◽

Diagnostic Techniques ◽

Pubmed Database ◽

Diagnostic Approaches

Alzheimer’s disease is a neurodegenerative condition associated with neurofibrillary tangles and cortical deposition of amyloid plaques. Clinical presentation of the disease involves manifestations such as memory loss, cognitive decline and dementia with some of the earliest reported deficits being episodic memory impairment and olfactory dysfunction. Current diagnostic approaches rely on autopsy characterization of gross brain pathology, or brain imaging of biomarkers late in the disease course. The aim of this literature review is to identify and compare newly emerging and novel CSF, serum and mucosal biomarkers, with the potential of making an earlier clinical diagnosis of Alzheimer’s disease. Utilizing such techniques may allow for earlier therapeutic intervention, reduction of disability and enhancement of quality of life. Literature review and analysis was performed by screening the PubMed database for relevant studies within the past 5 years. All studies showed statistically significant (P < 0.05) differences in testing between AD patients and controls. Two categories of serum biomarkers (redox-reactive antiphospholipid antibodies and microRNAs) and an olfactory mucosal marker (microRNA-206) could discriminate between early AD patients and controls with high sensitivity and specificity. In conclusion, certain studies have shown promising results with high sensitivity and specificity, high discriminative potential for Alzheimer’s disease early in its progression, and statistically significant results in larger study samples. Utilization of such diagnostic techniques should increase the efficacy of making an earlier clinical diagnosis of Alzheimer’s disease.

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Diagnosing Alzheimer’s Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe

Journal of Alzheimer s Disease ◽

10.3233/jad-215402 ◽

2021 ◽

pp. 1-14

Author(s):

Stefanie A.G. Black ◽

Anastasiia A. Stepanchuk ◽

George W. Templeton ◽

Yda Hernandez ◽

Tomoko Ota ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protein Misfolding ◽

Mononuclear Cells ◽

Immune Cell ◽

Amyloid Β ◽

Csf Biomarkers ◽

Blood Leukocytes ◽

Peripheral Blood Mononuclear ◽

The Brain

Background: Toxic amyloid-β (Aβ) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials. Objective: To develop a novel method for early Alzheimer’s disease (AD) detection, we used blood leukocytes, that could act as “sentinels” after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy. Methods: Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis. Results: K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aβ 42 and t-Tau metrics further improved the AUC to 0.93. Conclusion: Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease.

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Metabolomic Alterations in the Blood and Brain in Association with Alzheimer’s Disease: Evidence from in vivo to Clinical Studies

Journal of Alzheimer s Disease ◽

10.3233/jad-210737 ◽

2021 ◽

pp. 1-28

Author(s):

Sirawit Sriwichaiin ◽

Nipon Chattipakorn ◽

Siriporn C. Chattipakorn

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Studies ◽

Elderly Population ◽

The Elderly ◽

Pathological Findings ◽

Major Health Problem ◽

Major Health ◽

The Brain

Alzheimer’s disease (AD) has become a major health problem among the elderly population. Some evidence suggests that metabolic disturbance possibly plays a role in the pathophysiology of AD. Currently, the study of metabolomics has been used to explore changes in multiple metabolites in several diseases, including AD. Thus, the metabolomics research in AD might provide some information regarding metabolic dysregulations, and their possible associated pathophysiology. This review summarizes the information discovered regarding the metabolites in the brain and the blood from the metabolomics research of AD from both animal and clinical studies. Additionally, the correlation between the changes in metabolites and outcomes, such as pathological findings in the brain and cognitive impairment are discussed. We also deliberate on the findings of cohort studies, demonstrating the alterations in metabolites before changes of cognitive function. All of these findings can be used to inform the potential identity of specific metabolites as possible biomarkers for AD.

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Molecular and Imaging Biomarkers in Alzheimer’s Disease: A Focus on Recent Insights

Journal of Personalized Medicine ◽

10.3390/jpm10030061 ◽

2020 ◽

Vol 10 (3) ◽

pp. 61 ◽

Cited By ~ 1

Author(s):

Chiara Villa ◽

Marialuisa Lavitrano ◽

Elena Salvatore ◽

Romina Combi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Mechanisms ◽

Biological Fluids ◽

Imaging Techniques ◽

Amyloid Β ◽

The Elderly ◽

Diagnostic Methods ◽

Imaging Biomarkers ◽

Attractive Alternative

Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods rely on measures of amyloid-β (Aβ), phosphorylated (p-tau) and total tau (t-tau) protein levels in the cerebrospinal fluid (CSF) aided by advanced neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). However, the invasiveness of these procedures and the high cost restrict their utilization. Hence, biomarkers from biological fluids obtained using non-invasive methods and novel neuroimaging approaches provide an attractive alternative for the early diagnosis of AD. Such biomarkers may also be helpful for better understanding of the molecular mechanisms underlying the disease, allowing differential diagnosis or at least prolonging the pre-symptomatic stage in patients suffering from AD. Herein, we discuss the advantages and limits of the conventional biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.

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Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer’s disease

Nature Communications ◽

10.1038/s41467-019-12242-1 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 39

Author(s):

Xavier Hadoux ◽

Flora Hui ◽

Jeremiah K. H. Lim ◽

Colin L. Masters ◽

Alice Pébay ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hyperspectral Imaging ◽

Spectral Difference ◽

Non Invasive ◽

Potential Biomarker ◽

Negative Controls ◽

The Brain ◽

Independent Cohort

Abstract Studies of rodent models of Alzheimer’s disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aβ), may serve as surrogate markers of brain Aβ levels. As Aβ has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aβ. Significant differences in the retinal reflectance spectra are found between individuals with high Aβ burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aβ loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aβ in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aβ load.

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Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer’s disease

Science Advances ◽

10.1126/sciadv.aaz9360 ◽

2020 ◽

Vol 6 (43) ◽

pp. eaaz9360 ◽

Cited By ~ 1

Author(s):

Lenora Higginbotham ◽

Lingyan Ping ◽

Eric B. Dammer ◽

Duc M. Duong ◽

Maotian Zhou ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Wide Spectrum ◽

Csf Biomarkers ◽

Protein Biomarkers ◽

Cerebrospinal Fluid Biomarkers ◽

Brain Proteome ◽

The Brain ◽

Underlying Pathophysiology

Alzheimer’s disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified ~3500 and ~12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.

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