scholarly journals Biomarkers for Alzheimer’s Disease Early Diagnosis

2020 ◽  
Vol 10 (3) ◽  
pp. 114 ◽  
Author(s):  
Eva Ausó ◽  
Violeta Gómez-Vicente ◽  
Gema Esquiva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Loss ◽  
Diagnostic Tools ◽  
Csf Biomarkers ◽  
Diagnosis And Prognosis ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

Retinal Changes in Transgenic Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Li Guo ◽  
Nivedita Ravindran ◽  
Daniel Hill ◽  
M. Francesca Cordeiro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Immunohistochemical Analysis ◽  
Therapeutic Effects ◽  
The Central Nervous System ◽  
New Treatments ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder, the most common form of dementia. AD is characterized by amyloid-ß (Aß) plaques and neurofibrillary tangles (NFT) in the brain, in association with neuronal loss and synaptic failure, causing cognitive deficits. Accurate and early diagnosis is currently unavailable in lifespan, hampering early intervention of potential new treatments. Visual deficits have been well-documented in AD patients, and the pathological changes identified in the brain are also believed to be found in the retina, an integral part of the central nervous system. Retinal changes can be detected by real-time non-invasive imaging due to the transparent nature of the ocular media, potentially allowing an earlier diagnosis as well as monitoring disease progression and treatment outcome. Animal models are essential for AD research, and this review has a focus on retinal changes in various transgenic AD mouse models with retinal imaging and immunohistochemical analysis as well as therapeutic effects in those models. We also discuss the limitations of transgenic AD models in clinical translations.

The Associations of Serum Valine with Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
Author(s):  
Yong-lan Xiong ◽  
Joseph Therriault ◽  
Shu-jiang Ren ◽  
Xiao-jun Jing ◽  
Hua Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Glucose Metabolism ◽  
Rate Of Change ◽  
Cerebral Glucose Metabolism ◽  
Csf Biomarkers ◽  
Positron Emission ◽  
Magnetic Resonance Imaging Mri

Abstract The introduction of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in Alzheimer’s disease (AD). Recent studies have found that the levels of valine are related to mild cognitive impairment (MCI) and AD, but its characteristics in MCI and AD need to be further clarified. A total of 786 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort were selected to evaluate the relationships between serum valine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (18F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. We found that (1) serum valine was decreased in patients with AD compared with cognitive normal (CN) and stable MCI (sMCI), and in progressive MCI (pMCI) compared with CN; (2) serum valine was negatively correlated with CSF total tau (t-tau) and phosphorylated tau (p-tau) in pMCI; (3) serum valine significantly predicted conversion from MCI to AD; (4) serum valine was related to the rate of change of cerebral glucose metabolism during the follow-up period in pMCI. We speculated serum valine may be a peripheral biomarker of pMCI and AD, and its level predicts the progression of MCI to AD. Our study may help to reveal the metabolic changes during AD disease trajectory and its relationship to clinical phenotype.

scholarly journals Ceramide and Related-Sphingolipid Levels Are Not Altered in Disease-Associated Brain Regions of APPSLand APPSL/PS1M146LMouse Models of Alzheimer's Disease: Relationship with the Lack of Neurodegeneration?

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Laurence Barrier ◽  
Bernard Fauconneau ◽  
Anastasia Noël ◽  
Sabrina Ingrand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neuronal Death ◽  
Time Course ◽  
Neuronal Loss ◽  
Brain Regions ◽  
App Processing ◽  
Ceramide Accumulation ◽  
The Brain

There is evidence linking sphingolipid abnormalities, APP processing, and neuronal death in Alzheimer's disease (AD). We previously reported a strong elevation of ceramide levels in the brain of the APPSL/PS1Ki mouse model of AD, preceding the neuronal death. To extend these findings, we analyzed ceramide and related-sphingolipid contents in brain from two other mouse models (i.e., APPSLand APPSL/PS1M146L) in which the time-course of pathology is closer to that seen in most currently available models. Conversely to our previous work, ceramides did not accumulate in disease-associated brain regions (cortex and hippocampus) from both models. However, the APPSL/PS1Ki model is unique for its drastic neuronal loss coinciding with strong accumulation of neurotoxic Aβisoforms, not observed in other animal models of AD. Since there are neither neuronal loss nor toxic Aβspecies accumulation in APPSLmice, we hypothesized that it might explain the lack of ceramide accumulation, at least in this model.

scholarly journals A Large-scale Comparison of Cortical and Subcortical Structural Segmentation Methods in Alzheimer’s Disease: a Statistical Approach

2020 ◽  
Author(s):  
Jafar Zamani ◽  
Ali Sadr ◽  
Amir-Homayoun Javadi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Automated Segmentation ◽  
Resonance Imaging ◽  
Brain Areas ◽  
Segmentation Methods ◽  
Magnetic Resonance Imaging Mri ◽  
Underlying Mechanisms ◽  
The Brain

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that leads to anatomical atrophy, as evidenced by magnetic resonance imaging (MRI). Automated segmentation methods are developed to help with the segmentation of different brain areas. However, their reliability has yet to be fully investigated. To have a more comprehensive understanding of the distribution of changes in AD, as well as investigating the reliability of different segmentation methods, in this study we compared volumes of cortical and subcortical brain segments, using automated segmentation methods in more than 60 areas between AD and healthy controls (HC).MethodsA total of 44 MRI images (22 AD and 22 HC, 50% females) were taken from the minimal interval resonance imaging in Alzheimer’s disease (MIRIAD) dataset. HIPS, volBrain, CAT and BrainSuite segmentation methods were used for the subfields of hippocampus, and the rest of the brain.ResultsWhile HIPS, volBrain and CAT showed strong conformity with the past literature, BrainSuite misclassified several brain areas. Additionally, the volume of the brain areas that successfully discriminated between AD and HC showed a correlation with mini mental state examination (MMSE) scores. The two methods of volBrain and CAT showed a very strong correlation. These two methods, however, did not correlate with BrainSuite.ConclusionOur results showed that automated segmentation methods HIPS, volBrain and CAT can be used in the classification of AD and HC. This is an indication that such methods can be used to inform researchers and clinicians of underlying mechanisms and progression of AD.

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

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.

scholarly journals The Diagnosis of Alzheimer’s Disease: An Ensemble Approach

2020 ◽  
Author(s):  
Jingyan Qiu ◽  
Linjian Li ◽  
Yida Liu ◽  
Yingjun Ou ◽  
Yubei Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Learning ◽  
Large Scale ◽  
Early Stage ◽  
Training Transfer ◽  
Detection And Diagnosis ◽  
Magnetic Resonance Imaging Mri ◽  
Deep Learning Model ◽  
The Brain

Alzheimer’s disease (AD) is one of the most common forms of dementia. The early stage of the disease is defined as Mild Cognitive Impairment (MCI). Recent research results have shown the prospect of combining Magnetic Resonance Imaging (MRI) scanning of the brain and deep learning to diagnose AD. However, the CNN deep learning model requires a large scale of samples for training. Transfer learning is the key to enable a model with high accuracy by using limited data for training. In this paper, DenseNet and Inception V4, which were pre-trained on the ImageNet dataset to obtain initialization values of weights, are, respectively, used for the graphic classification task. The ensemble method is employed to enhance the effectiveness and efficiency of the classification models and the result of different models are eventually processed through probability-based fusion. Our experiments were completely conducted on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) public dataset. Only the ternary classification is made due to a higher demand for medical detection and diagnosis. The accuracies of AD/MCI/Normal Control (NC) of different models are estimated in this paper. The results of the experiments showed that the accuracies of the method achieved a maximum of 92.65%, which is a remarkable outcome compared with the accuracies of the state-of-the-art methods.

Neuroimaging in Alzheimer’s Disease

2013 ◽  
pp. 427-431 ◽  
Author(s):  
Hidenao Fukuyama
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Posterior Part ◽  
Lewy Body Disease ◽  
New Drugs ◽  
Amyloid Protein ◽  
Dementia Patients ◽  
Positron Emission ◽  
Occipital Lobes ◽  
The Brain

The diagnosis of Alzheimer’s disease (AD) is often based on clinical and pathological data. Positron emission tomography (PET) using the tracer 18F-FDG revealed findings specific to AD-mainly the posterior part of the brain and the association cortices of the parietal and occipital lobes were affected by a reduction in glucose metabolism. Recent advances in the development of tracers for amyloid protein, which is the key protein in the pathogenesis of AD, enables the pattern of deposition of amyloid protein in the brain to be visualized. Various tracers have been introduced to visualize other aspects of AD pathology. Recent clinical interests on dementia have focused on the early detection of AD and variation of Parkinson’s disease, namely dementia with Lewy body disease (DLB), because the earlier the diagnosis, the better the prognosis. The differential diagnosis of mild AD or mild cognitive impairment (MCI) as well as DLB has been studied using PET and MRI as part of the NIH’s Alzheimer disease Neuroimaging initiative (ADNI). At present, many countries are participating in the ADNI, which is yielding promising results. This chapter’s study will improve the development of new drugs for the treatment of dementia patients by enabling the evaluation of the effect and efficacy of those drugs.

scholarly journals Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 982
Author(s):  
Cassis Varlow ◽  
Emily Murrell ◽  
Jason P. Holland ◽  
Alina Kassenbrock ◽  
Whitney Shannon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Radiochemical Yield ◽  
Sulfonium Salt ◽  
Model Of Alzheimer’S Disease ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Early Biomarker ◽  
Pet Radiopharmaceutical ◽  
Abundance And Distribution

[18F]FPEB is a positron emission tomography (PET) radiopharmaceutical used for imaging the abundance and distribution of mGluR5 in the central nervous system (CNS). Efficient radiolabeling of the aromatic ring of [18F]FPEB has been an ongoing challenge. Herein, five metal-free precursors for the radiofluorination of [18F]FPEB were compared, namely, a chloro-, nitro-, sulfonium salt, and two spirocyclic iodonium ylide (SCIDY) precursors bearing a cyclopentyl (SPI5) and a new adamantyl (SPIAd) auxiliary. The chloro- and nitro-precursors resulted in a low radiochemical yield (<10% RCY), whereas both SCIDY precursors and the sulfonium salt precursor produced [18F]FPEB in the highest RCYs of 25% and 36%, respectively. Preliminary PET/CT imaging studies with [18F]FPEB were conducted in a transgenic model of Alzheimer’s Disease (AD) using B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) mice, and data were compared with age-matched wild-type (WT) B6C3F1/J control mice. In APP/PS1 mice, whole brain distribution at 5 min post-injection showed a slightly higher uptake (SUV = 4.8 ± 0.4) than in age-matched controls (SUV = 4.0 ± 0.2). Further studies to explore mGluR5 as an early biomarker for AD are underway.

scholarly journals Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Better Than

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

scholarly journals Perspective of SGLT2 Inhibition in Treatment of Conditions Connected to Neuronal Loss: Focus on Alzheimer’s Disease and Ischemia-Related Brain Injury

2020 ◽  
Vol 13 (11) ◽  
pp. 379
Author(s):  
Michał Wiciński ◽  
Eryk Wódkiewicz ◽  
Karol Górski ◽  
Maciej Walczak ◽  
Bartosz Malinowski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Damage ◽  
Neurovascular Unit ◽  
Neuronal Loss ◽  
Impact Risk ◽  
Sglt2 Inhibition ◽  
The Central Nervous System ◽  
Cortical Regions ◽  
Endothelial Growth Factor

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are oral anti-hyperglycemic agents approved for the treatment of type 2 diabetes mellitus. Some reports suggest their presence in the central nervous system and possible neuroprotective properties. SGLT2 inhibition by empagliflozin has shown to reduce amyloid burden in cortical regions of APP/PS1xd/db mice. The same effect was noticed regarding tau pathology and brain atrophy volume. Empagliflozin presented beneficial effect on cognitive function, which may be connected to an increase in cerebral brain-derived neurotrophic factor. Canagliflozin and dapagliflozin may possess acetylcholinesterase inhibiting activity, resembling in this matter Alzheimer’s disease-registered therapies. SGLT2 inhibitors may prove to impact risk factors of atherosclerosis and pathways participating both in acute and late stage of stroke. Their mechanism of action can be related to induction in hepatocyte nuclear factor-1α, vascular endothelial growth factor-A, and proinflammatory factors limitation. Empagliflozin may have a positive effect on preservation of neurovascular unit in diabetic mice, preventing its aberrant remodeling. Canagliflozin seems to present some cytostatic properties by limiting both human and mice endothelial cells proliferation. The paper presents potential mechanisms of SGLT-2 inhibitors in conditions connected with neuronal damage, with special emphasis on Alzheimer’s disease and cerebral ischemia.

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