scholarly journals Olfactory response as a marker for Alzheimer’s disease: Evidence from perceptual and frontal lobe oscillation coherence deficit

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243535
Author(s):  
Mohammad Javad Sedghizadeh ◽  
Hadi Hojjati ◽  
Kiana Ezzatdoost ◽  
Hamid Aghajan ◽  
Zahra Vahabi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Cortex ◽  
High Frequency ◽  
Medial Temporal Lobe ◽  
Spatial Coherence ◽  
Olfactory Stimulation ◽  
Olfactory Perception ◽  
Potential Biomarker ◽  
The Brain

High-frequency oscillations of the frontal cortex are involved in functions of the brain that fuse processed data from different sensory modules or bind them with elements stored in the memory. These oscillations also provide inhibitory connections to neural circuits that perform lower-level processes. Deficit in the performance of these oscillations has been examined as a marker for Alzheimer’s disease (AD). Additionally, the neurodegenerative processes associated with AD, such as the deposition of amyloid-beta plaques, do not occur in a spatially homogeneous fashion and progress more prominently in the medial temporal lobe in the early stages of the disease. This region of the brain contains neural circuitry involved in olfactory perception. Several studies have suggested that olfactory deficit can be used as a marker for early diagnosis of AD. A quantitative assessment of the performance of the olfactory system can hence serve as a potential biomarker for Alzheimer’s disease, offering a relatively convenient and inexpensive diagnosis method. This study examines the decline in the perception of olfactory stimuli and the deficit in the performance of high-frequency frontal oscillations in response to olfactory stimulation as markers for AD. Two measurement modalities are employed for assessing the olfactory performance: 1) An interactive smell identification test is used to sample the response to a sizable variety of odorants, and 2) Electroencephalography data are collected in an olfactory perception task with a pair of selected odorants in order to assess the connectivity of frontal cortex regions. Statistical analysis methods are used to assess the significance of selected features extracted from the recorded modalities as Alzheimer’s biomarkers. Olfactory decline regressed to age in both healthy and mild AD groups are evaluated, and single- and multi-modal classifiers are also developed. The novel aspects of this study include: 1) Combining EEG response to olfactory stimulation with behavioral assessment of olfactory perception as a marker of AD, 2) Identification of odorants most significantly affected in mild AD patients, 3) Identification of odorants which are still adequately perceived by mild AD patients, 4) Analysis of the decline in the spatial coherence of different oscillatory bands in response to olfactory stimulation, and 5) Being the first study to quantitatively assess the performance of olfactory decline due to aging and AD in the Iranian population.

scholarly journals Olfactory Response as a Marker for Alzheimer's Disease: Evidence from Perceptual and Frontal Oscillation Coherence Deficit

2019 ◽  
Author(s):  
Mohammad Javad Sedghizadeh ◽  
Hadi Hojjati ◽  
Kiana Ezzatdoost ◽  
Hamid Aghajan ◽  
Zahra Vahabi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Cortex ◽  
High Frequency ◽  
Medial Temporal Lobe ◽  
Spatial Coherence ◽  
Olfactory Stimulation ◽  
Olfactory Perception ◽  
Potential Biomarker ◽  
The Brain

High-frequency oscillations of the frontal cortex are involved in functions of the brain that fuse processed data from different sensory modules or bind them with elements stored in the memory. These oscillations also provide inhibitory connections to neural circuits that perform lower-level processes. Deficit in the performance of these oscillations has been examined as a marker for Alzheimer's disease (AD). Additionally, the neurodegenerative processes associated with AD, such as the deposition of amyloid-beta plaques, do not occur in a spatially homogeneous fashion and progress more prominently in the medial temporal lobe in the early stages of the disease. This region of the brain contains neural circuitry involved in olfactory perception. Several studies have suggested that olfactory deficit can be used as a marker for early diagnosis of AD. A quantitative assessment of the performance of the olfactory system can hence serve as a potential biomarker for Alzheimer's disease, offering a relatively convenient and inexpensive diagnosis method. This study examines the decline in the perception of olfactory stimuli and the deficit in the performance of high-frequency frontal oscillations in response to olfactory stimulation as markers for AD. Two measurement modalities are employed for assessing the olfactory performance: 1) An interactive smell identification test is used to sample the response to a sizable variety of odorants, and 2) Electrophysiological data are collected in an olfactory perception task with a pair of selected odorants in order to assess the connectivity of frontal cortex regions. Statistical analysis methods are used to assess the significance of selected features extracted from the recorded modalities as Alzheimer's biomarkers. Olfactory decline regressed to age in both healthy and Mild AD groups are evaluated, and single- and multi-modal classifiers are also developed. The novel aspects of this study include: 1) Combining EEG response to olfactory stimulation with behavioral assessment of olfactory perception as a marker of AD, 2) Identification of odorants most significantly affected in Mild AD patients, 3) Identification of odorants which are still adequately perceived by Mild AD patients, 4) Analysis of the decline in the spatial coherence of different oscillatory bands in response to olfactory stimulation, and 5) Being the first study to quantitatively assess the performance of olfactory decline due to aging and AD in the Iranian population.

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

2019 ◽  
Vol 10 (1) ◽  
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.

scholarly journals Imaging asparaginyl endopeptidase (AEP) in the live brain as a biomarker for Alzheimer’s disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shan-Shan Wang ◽  
Zi-Kai Liu ◽  
Jing-Jing Liu ◽  
Qing Cheng ◽  
Yan-Xia Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Senile Plaques ◽  
Disease Stage ◽  
Assay Method ◽  
Imaging Probe ◽  
Asparaginyl Endopeptidase ◽  
Potential Biomarker ◽  
The Brain

Abstract Background Discovery of early-stage biomarkers is a long-sought goal of Alzheimer’s disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn’t proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology. Results This AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala–Ala–Asn–Cys–Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg−1, p.o.) reduced production of β-amyloid (Aβ) and ameliorated memory loss. Therefore, elevation of AEP is an early sign of AD onset. Finally, we showed that live animal imaging with this AEP-responsive probe could monitor the up-regulated AEP in the brain of APP/PS1 mice. Conclusions The current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD. Graphical abstract

scholarly journals Ceruloplasmin/Transferrin Ratio Changes in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Rosanna Squitti ◽  
Carlo Salustri ◽  
Mariacristina Siotto ◽  
Mariacarla Ventriglia ◽  
Fabrizio Vernieri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Serum Iron ◽  
Transferrin Saturation ◽  
Serum Levels ◽  
Medial Temporal Lobe Atrophy ◽  
The Brain ◽  
Lobe Atrophy ◽  
Local Accumulation

The link between iron and Alzheimer's disease (AD) has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf). Cp/Tf and transferrin saturation increased in AD patients. Cp/Tf ratios also correlated positively with peroxide levels and negatively with serum iron concentrations. Elevated values of ceruloplasmin, peroxides, and Cp/Tf inversely correlated with MMSE scores. Isolated medial temporal lobe atrophy positively correlated with Cp/Tf and negatively with serum iron. All these findings indicate that the local iron accumulation found in brain areas critical for AD should be viewed in the frame of iron systemic alterations.

scholarly journals Elevated CSF LRG and Decreased Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Vol 10 (5) ◽  
pp. 1105
Author(s):  
Aleksi Vanninen ◽  
Madoka Nakajima ◽  
Masakazu Miyajima ◽  
Tuomas Rauramaa ◽  
Merja Kokki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Normal Pressure Hydrocephalus ◽  
Brain Biopsy ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Potential Biomarker ◽  
Shunt Response ◽  
T Tau ◽  
The Brain

Leucine-rich-alpha-2-glykoprotein (LRG) is suggested as a potential biomarker for idiopathic normal pressure hydrocephalus (iNPH). Our goal was to compare the cerebrospinal fluid (CSF) LRG levels between 119 iNPH patients and 33 age-matched controls and with the shunt responses and the brain biopsy Alzheimer’s disease (AD) pathology among the iNPH patients. CSF LRG, Aβ1-42, P-tau181, and T-tau were measured by using commercial ELISAs. The LRG levels in the CSF were significantly increased in the iNPH patients (p < 0.001) as compared to the controls, regardless of the AD pathology. However, CSF LRG did not correlate with the shunt response in contrast to the previous findings. The CSF AD biomarkers, i.e., Aβ1-42, T-tau, and P-tau correlated with the brain biopsy AD pathology as expected but were systematically lower in the iNPH patients when compared to the controls (<0.001). Our findings support that the LRG levels in the CSF are potentially useful for the diagnostics of iNPH, independent of the brain AD pathology, but contrary to previous findings, not for predicting the shunt response. Our findings also suggest a need for specific reference values of the CSF AD biomarkers for the diagnostics of comorbid AD pathology in the iNPH patients.

Predicting Alzheimer's Disease Based on Network Topological Latent Representations

2020 ◽  
Vol 10 (3) ◽  
pp. 667-671
Author(s):  
Jing Sun ◽  
Yanhui Ding ◽  
Kun Zhao ◽  
Haiyan Xu ◽  
Yongxin Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Parietal Lobe ◽  
Structural Features ◽  
Brain Network ◽  
Feature Representation ◽  
Support Vector ◽  
Functional Connection ◽  
Potential Biomarker ◽  
The Brain

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Right now there is no cure for AD. As we know, the brain structure is constantly changing as it progresses to AD. If we can detect these changes, it may be helpful to discover new biomarkers and early diagnosis of AD. We use the deep learning method DeepWalk to extract the structural features of each subject based on brain function connection. The method takes a brain topology network based on functional connection transformations as input and outputs a potential feature representation for each brain region in the brain network structure. In the current research, a new potential biomarker is found, which is based on a structural feature that can represent changes in brain connectivity. In our experiment, 79 Resting-state fMRI were used from ADNI dataset, including 49 normal controls (NCs) and 30 AD patients. By analyzing the structural features between AD patients and NCs, obvious differences are detected in the temporal lobe, parietal lobe, and frontal lobe. We use a support vector machine (SVM) model to evaluate the performance of these structural features, and its classification performance achieves 80.36% accuracy (specificity = 73.67%, sensitivity = 87.17%). In general, these findings indicate that structural features may be a new potential biomarker between NCs and AD patients.

scholarly journals Promising Genetic Biomarkers of Preclinical Alzheimer's Disease: The Influence ofAPOEandTOMM40on Brain Integrity

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Beata Ferencz ◽  
Sari Karlsson ◽  
Grégoria Kalpouzos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Imaging Techniques ◽  
Preclinical Alzheimer’S Disease ◽  
Brain Areas ◽  
Structural Alterations ◽  
Genetic Biomarkers ◽  
Preclinical Ad ◽  
The Brain

Finding biomarkers constitutes a crucial step for early detection of Alzheimer's disease (AD). Brain imaging techniques have revealed structural alterations in the brain that may be phenotypic in preclinical AD. The most prominent polymorphism that has been associated with AD and related neural changes is the Apolipoprotein E (APOE)ε4. The translocase of outer mitochondrial membrane 40 (TOMM40), which is in linkage disequilibrium withAPOE, has received increasing attention as a promising gene in AD.TOMM40also impacts brain areas vulnerable in AD, by downstream apoptotic processes that forego extracellular amyloid beta aggregation. The present paper aims to extend on the mitochondrial influence in AD pathogenesis and we propose aTOMM40-induced disconnection of the medial temporal lobe. Finally, we discuss the possibility of mitochondrial dysfunction being the earliest pathophysiological event in AD, which indeed is supported by recent findings.

Predicting Alzheimer's Disease Based on Network Topological Latent Representations

2020 ◽  
Vol 10 (3) ◽  
pp. 667-671
Author(s):  
Jing Sun ◽  
Yanhui Ding ◽  
Kun Zhao ◽  
Haiyan Xu ◽  
Yongxin Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Parietal Lobe ◽  
Structural Features ◽  
Brain Network ◽  
Feature Representation ◽  
Support Vector ◽  
Functional Connection ◽  
Potential Biomarker ◽  
The Brain

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Right now there is no cure for AD. As we know, the brain structure is constantly changing as it progresses to AD. If we can detect these changes, it may be helpful to discover new biomarkers and early diagnosis of AD. We use the deep learning method DeepWalk to extract the structural features of each subject based on brain function connection. The method takes a brain topology network based on functional connection transformations as input and outputs a potential feature representation for each brain region in the brain network structure. In the current research, a new potential biomarker is found, which is based on a structural feature that can represent changes in brain connectivity. In our experiment, 79 Resting-state fMRI were used from ADNI dataset, including 49 normal controls (NCs) and 30 AD patients. By analyzing the structural features between AD patients and NCs, obvious differences are detected in the temporal lobe, parietal lobe, and frontal lobe. We use a support vector machine (SVM) model to evaluate the performance of these structural features, and its classification performance achieves 80.36% accuracy (specificity = 73.67%, sensitivity = 87.17%). In general, these findings indicate that structural features may be a new potential biomarker between NCs and AD patients.

scholarly journals The Therapeutic Targets of Fingolimod (FTY720) Are Involved in Pathological Processes in the Frontal Cortex of Alzheimer's Disease Patients: A Network Pharmacology Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Pengqi Yin ◽  
Yang Xue ◽  
Tingting Wang ◽  
Di Zhong ◽  
Guozhong Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Cortex ◽  
Brain Tissue ◽  
Disease Severity ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Network Pharmacology ◽  
Immune Cell Infiltration ◽  
The Brain

Background: The sphingosine-1-phosphate receptor (S1PR) modulator fingolimod (FTY720), which is commonly used as an immunomodulator in multiple sclerosis treatment, has recently been found to reduce pathological changes in the brain tissue of Alzheimer's disease (AD) animal models, but this has yet to be verified in human brain tissue. In this study, network pharmacology methods were applied to determine the potential pharmacological mechanisms of fingolimod in the frontal cortex of AD patients.Methods: The pharmacological macromolecular targets of fingolimod and fingolimod phosphate were downloaded from SwissTarget and DrugBank. Systematic intersection analysis of the expression profiles of brain frontal cortex tissues (423 AD tissues and 266 control tissues) was performed to obtain AD-associated fingolimod targets (F-ADGs). Immune cell infiltration analysis and a primary mouse cortical culture RNA-seq drug screen database were used to identify immune-related F-ADGs and cortex-related F-ADGs. Then, the expression values of F-ADGs were correlated with the disease severity score (MMSE score) of AD patients to identify severity-related F-ADGs. We also analyzed miRNA expression microarray data in the frontal cortex of AD patients associated with disease severity to obtain severity-related F-ADG-miRNAs.Results: A total of 188 F-ADGs were detected in the frontal cortices of AD patients and were enriched in biological processes such as synaptic signaling, inflammatory response, and response to oxygen-containing compounds. Eleven immune-related F-ADGs (like FPR1, BLNK.) and 17 cortex-related F-ADGs (like ALDH1L1, DUSP1.) were detected. Other F-ADGs, such as S1PR1 and GABBR2, although not classified into the above two categories, were still predicted by bioinformatics methods to play an important role in the development of AD. Two F-ADGs (GNAQ and MMP14) and 28 miRNAs (like miR- 323a-3p, miR-181a-5p.) were found to be associated with AD severity (MMSE 0-27 group). Fifteen F-ADGs (like ALDH1L1, FPR1, and IL6.) and 46 miRNAs (like miR-212-5p, miR-93-5p.) were found to be associated with mild or moderate dementia AD patients' severity (MMSE11-22 subgroup).Conclusions: Fingolimod may affect the brain frontal cortex function of AD patients in many different ways, such as affecting immune cell infiltration, nerve cell, or glial cell function, and synaptic function. miRNAs may also be involved. ALDH1L1, FPR1, S1PR1, and GABBR2 may be core drug targets.

scholarly journals Differential effects of statins and alendronate on cholinesterases in serum and brain of rats

2007 ◽  
pp. 765-770
Author(s):  
L Cibičková ◽  
V Palička ◽  
N Cibiček ◽  
E Čermáková ◽  
S Mičuda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Cortex ◽  
Blood Brain Barrier ◽  
Ache Activity ◽  
Acetylcholinesterase Activity ◽  
Brain Barrier ◽  
Ache Inhibitors ◽  
Blood Brain ◽  
The Brain

Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer's disease. Cholesterol plays an important role in Alzheimer's disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl- nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug.

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