scholarly journals Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer’s Disease

2019 ◽  
Vol 21 (1) ◽  
pp. 70
Author(s):  
María Sánchez-Campillo ◽  
María José Ruiz-Pastor ◽  
Antonio Gázquez ◽  
Juan Marín-Muñoz ◽  
Fuensanta Noguera-Perea ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Blood ◽  
Neurodegenerative Disorder ◽  
Major Facilitator Superfamily ◽  
Postmortem Brain ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Major Facilitator ◽  
First Time

The protein Major Facilitator Superfamily Domain containing 2A (MFSD2a) was recently described as the primary carrier for docosahexaenoic acid (DHA) into the brain. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by lower DHA levels in blood lipids. The aim of this study was to investigate the expression of MFSD2a in the whole blood and brain as a potential biomarker of AD. Three groups were established: 38 healthy controls, 48 subjects with moderate AD (GDS4), and 47 with severe AD (GDS6). We analyzed postmortem brain samples from the hippocampus of 11 healthy controls and 11 severe AD patients. Fatty acid (FA) was determined in serum and brain by gas chromatography. Blood and brain MFSD2a protein expression was analyzed by Western blotting. We found a significant and progressive decline of MFSD2a levels in blood of AD patients (Control 0.83 ± 0.13, GDS4 0.72 ± 0.09, GDS6 0.48 ± 0.05*, p ˂ 0.01). We also corroborated a significant reduction of DHA and other n-3 long-chain polyunsaturated FA in serum of AD. No differences were found in MFSD2a expression or FA levels in brain of controls and AD subjects. MFSD2A carrier was analyzed in AD patients for the first time and the level of MFSD2a in the whole blood could be a potential biomarker of this disease.

scholarly journals YKL-40 as a Potential Biomarker for the Differential Diagnosis of Alzheimer’s Disease

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 60
Author(s):  
Ioannis Mavroudis ◽  
Rumana Chowdhury ◽  
Foivos Petridis ◽  
Eleni Karantali ◽  
Symela Chatzikonstantinou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Cochrane Library ◽  
Potential Biomarker ◽  
The Cochrane Library

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, associated with extensive neuronal loss, dendritic and synaptic changes resulting in significant cognitive impairment. An increased number of studies have given rise to the neuroinflammatory hypothesis in AD. It is widely accepted that AD brains show chronic inflammation, probably triggered by the presence of insoluble amyloid beta deposits and neurofibrillary tangles (NFT) and is also related to the activation of neuronal death cascade. In the present study we aimed to investigate the role of YKL-40 levels in the cerebrospinal fluid (CSF) in the diagnosis of AD, and to discuss whether there are further potential roles of this protein in the management and treatment of AD. We conducted an online search on PubMed, Web of Science, and the Cochrane library databases from 1990 to 2021. The quantitative analysis showed that the levels of YKL-40 were significantly higher in Alzheimer’s disease compared to controls, to mild cognitive impairment (MCI) AD (MCI-AD) and to stable MCI. They were also increased in MCI-AD compared to stable MCI. The present study shows that the CSF levels of YKL-40 could be potentially used as a biomarker for the prognosis of mild cognitive impairment and the likelihood of progression to AD, as well as for the differential diagnosis between AD and MCI.

scholarly journals Investigation of five polymorphic DNA markers associated with late onset Alzheimer disease

Genetika ◽  
2013 ◽  
Vol 45 (2) ◽  
pp. 503-514 ◽  
Author(s):  
Jalal Gharesouran ◽  
Maryam Rezazadeh ◽  
Mohaddes Mojtaba
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Markers ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
The Elderly ◽  
Healthy Controls ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
And Control

Alzheimer's disease is a complex neurodegenerative disorder characterized by memory and cognitive impairment and is the leading cause of dementia in the elderly. The aim of our study was to examine the polymorphic DNA markers CCR2 (+190 G/A), CCR5?32, TNF-? (-308 G/A), TNF-? (-863 C/A) and CALHM1 (+394 C/T) to determine the relationship between these polymorphisms and the risk of late onset Alzheimer's disease in the population of Eastern Azerbaijan of Iran. A total of 160 patient samples and 163 healthy controls were genotyped by PCR-RFLP and the results confirmed using bidirectional sequencing. Statistical analysis of obtained data revealed non-significant difference between frequency of CCR5?32 in case and control groups. The same result was observed for TNF-? (-863 C/A) genotype and allele frequencies. Contrary to above results, significant differences were detected in frequency of TNF-? (-308 G/A) and CCR2-64I genotypes between the cases and healthy controls. A weak significant difference observed between allele and genotype frequencies of rs2986017 in CALHM1 (+394 C/T; P86L) in patient and control samples. It can be concluded that the T allele of P86L variant in CALHM1 & +190 G/A allele of CCR2 have a protective role against abnormal clinical features of Alzheimer's disease.

scholarly journals Altered Blood Levels of Anti-Gal Antibodies in Alzheimer’s Disease: A New Clue to Pathogenesis?

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 538
Author(s):  
Antonella Angiolillo ◽  
Alessandro Gandaglia ◽  
Alessia Arcaro ◽  
Andrea Carpi ◽  
Fabrizio Gentile ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Plaque ◽  
Amyloid Peptide ◽  
Blood Levels ◽  
Potential Link ◽  
Altered Blood ◽  
New Biomarkers ◽  
First Time

Alzheimer’s disease is a neurodegenerative disorder whose pathological mechanisms, despite recent advances, are not fully understood. However, the deposition of beta amyloid -peptide and neuroinflammation, which is probably aggravated by dysbiotic microbiota, seem to play a key role. Anti-Gal are the most abundant xenoreactive natural antibodies. They are supposed to stem from immunization against the gut microbiota and have been implicated in the pathogenesis of several diseases, including multiple sclerosis. These antibodies target the alpha-Gal epitope, expressed on the terminal sugar units of glycoprotein or glycolipid of all mammals except apes, Old World monkeys and humans. The alpha-Gal is constitutively expressed in several bacteria constituting the brain microbiota, and alpha-Gal-like epitopes have been detected in gray matter, amyloid plaque, neurofibrillary tangles and corpora amylacea of the human brain, suggesting a potential link between anti-Gal and Alzheimer’s disease etiopathogenesis. For the first time, our study searched for possible alterations of anti-Gal immunoglobulin levels in Alzheimer’s disease patients. IgG and IgM blood levels were significantly lower, and IgA significantly higher in patients than in healthy subjects. These results suggest that such immunoglobulins might be implicated in Alzheimer’s disease pathogenesis and open new scenarios in the research for new biomarkers and therapeutic strategies.

scholarly journals Aberrant White Matter Microstructure as a Potential Diagnostic Marker in Alzheimer’s Disease by Automated Fiber Quantification

2020 ◽  
Author(s):  
Haifeng Chen ◽  
Ruomeng Qin ◽  
Caimei Luo ◽  
Mengchun Li ◽  
Renyuan Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Neurodegenerative Disorder ◽  
Local Level ◽  
Uncinate Fasciculus ◽  
Fiber Tracts ◽  
White Matter Microstructure ◽  
Potential Biomarker ◽  
Anterior Thalamic Radiation

Abstract Background: Alzheimer’s disease (AD) has been primarily considered a progressive neurodegenerative disorder of gray matter. Neuroimaging evidence has suggested white matter microstructure are also heavily affected in AD. However, whether white matter dysfunction are localized at the specific regions of fiber tracts and whether they would be a potential biomarker for AD remain unclear.Methods：By automated fiber quantification (AFQ), we applied diffusion tensor images from 25 healthy controls (HC), 24 amnestic mild cognitive impairment (aMCI) patients and 18 AD patients to create tract profiles along 16 major white matter fibers. We compared diffusion metrics [Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA) and radial diffusivity (DR)] at the global and local level of fiber tracts between groups. Partial correlation analyses were used to explore the associations between white matter changes and cognitive performance. To assess the diagnostic value, we enrolled the significantly altered diffusion metrics into a random forest (RF) classifier, a type of machine learning method.Results: In the global tract level, we found that aMCI and AD patients showed higher MD, DA and DR values in some fiber tracts mostly in the left hemisphere compared to HC. In the point-wise level, widespread disruption were distributed on specific locations of different tracts. The point-wise MD measurements presented the best classification performance with respect to differentiating AD from HC. The two most important variables were localized in the prefrontal potion of left uncinate fasciculus and anterior thalamic radiation. In addition, the point-wise DA in the posterior component of the left cingulum cingulate displayed the most robust discriminative ability to identify AD from aMCI. Conclusion：Our findings provide evidence that the left-sided microstructural integrity was vulnerable in white matter fiber tracts in AD. Furthermore, the frontal lobe portion of left uncinate fasciculus and anterior thalamic radiation and the posterior component of the left cingulum cingulate played the important role in the diagnosis and surveillance of AD. These results demonstrated the potential of white matter abnormalities as a diagnostic biomarker in AD.

scholarly journals Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer’s Disease-Like Rats via PP2A/GSK-3β Signaling Pathway in Their Hippocampus

2019 ◽  
Vol 20 (8) ◽  
pp. 1871 ◽  
Author(s):  
Samaila Musa Chiroma ◽  
Mohamad Taufik Hidayat Baharuldin ◽  
Che Norma Mat Taib ◽  
Zulkhairi Amom ◽  
Saravanan Jagadeesan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Functions ◽  
Neurodegenerative Disorder ◽  
Glycogen Synthase ◽  
Centella Asiatica ◽  
The Elderly ◽  
Aluminium Chloride ◽  
Gsk 3Β ◽  
First Time

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat’s hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.

scholarly journals Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laure-Elise Pillet ◽  
Camille Taccola ◽  
Justine Cotoni ◽  
Hervé Thiriez ◽  
Karine André ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mini Mental State Examination ◽  
Disease Evolution ◽  
Noradrenaline Level ◽  
Potential Biomarker ◽  
Blood Marker ◽  
Plasma Noradrenaline Level ◽  
First Time ◽  
State Examination

AbstractRecent evidence showing degeneration of the noradrenergic system in the locus coeruleus (LC) in Alzheimer’s disease (AD) has motivated great interest in noradrenaline (NA) as a potential brain hallmark of the disease. Despite the current exploration of blood markers for AD, the deregulation of the plasma NA concentration ([NA]plasma) in AD is currently not well understood. This retrospective study includes a cohort of 71 patients (32 AD patients, 22 with other dementia and 17 without dementia) who were given consultations for memory complaints in the Cognitive Neurology Center of Lariboisière (Paris) between 2009 and 2014. As previously described in brain tissue, we show for the first time a linear correlation between [NA]plasma and Mini Mental State Examination (MMSE) score in AD patients. We observed that high [NA]plasma in AD patients was associated with higher [Aβ1–42]CSF than in other AD patients with [NA]plasma similar to NC patients. In parallel, we observed a lower (p-Tau/Tau)CSF in AD patients with low [NA]plasma than in non-AD patients with [NA]plasma similar to [NA]plasma in NC patients. Our data suggest that [NA]plasma could be a potential biomarker of disease evolution in the context of AD and could possibly improve early diagnosis.

scholarly journals Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 644 ◽  
Author(s):  
Cristina Fernández-Mendívil ◽  
Miguel A. Arreola ◽  
Lindsay A. Hohsfield ◽  
Kim N. Green ◽  
Manuela G. Lopez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Beta Amyloid ◽  
Postmortem Brain ◽  
Heme Oxygenase 1 ◽  
Total Brain ◽  
Potential Biomarker ◽  
Brain Expression ◽  
5Xfad Mice

Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties, while microglia are the immune cells in the central nervous system. To elucidate the brain expression profile of microglial HO-1 in aging and AD-progression, we have used the 5xFAD (five familial AD mutations) mouse model of AD and their littermates at different ages (four, eight, 12, and 18 months). Total brain expression of HO-1 was increased with aging and such increase was even higher in 5xFAD animals. In co-localization studies, HO-1 expression was mainly found in microglia vs. other brain cells. The percentage of microglial cells expressing HO-1 and the amount of HO-1 expressed within microglia increased progressively with aging. Furthermore, this upregulation was increased by 2–3-fold in the elder 5xFAD mice. In addition, microglia overexpressing HO-1 was predominately found surrounding beta-amyloid plaques. These results were corroborated using postmortem brain samples from AD patients, where microglial HO-1 was found up-regulated in comparison to brain samples from aged matched non-demented patients. This study demonstrates that microglial HO-1 expression increases with aging and especially with AD progression, highlighting HO-1 as a potential biomarker or therapeutic target for AD.

scholarly journals Word-Embeddings and Grammar Features to Detect Language Disorders in Alzheimer’s Disease Patients

TecnoLógicas ◽  
2020 ◽  
Vol 23 (47) ◽  
pp. 63-75
Author(s):  
Juan S. Guerrero-Cristancho ◽  
Juan C. Vásquez-Correa ◽  
Juan R. Orozco-Arroyave
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Language Production ◽  
Neurodegenerative Disorder ◽  
Word Embedding ◽  
Normal Brain ◽  
Healthy Controls ◽  
Feature Sets ◽  
Early Fusion ◽  
Frequency Features

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects the language production and thinking capabilities of patients. The integrity of the brain is destroyed over time by interruptions in the interactions between neuron cells and associated cells required for normal brain functioning. AD comprises deterioration of the communicative skills, which is reflected in deficient speech that usually contains no coherent information, low density of ideas, and poor grammar. Additionally, patients exhibit difficulties to find appropriate words to structure sentences. Multiple ongoing studies aim to detect the disease considering the deterioration of language production in AD patients. Natural Language Processing techniques are employed to detect patterns that can be used to recognize the language impairments of patients. This paper covers advances in pattern recognition with the use of word-embedding and word-frequency features and a new approach with grammar features. We processed transcripts of 98 AD patients and 98 healthy controls in the Pitt Corpus of the Dementia-Bank database. A total of 1200 word-embedding features, 1408 Term Frequency—Inverse Document Frequency features, and 8 grammar features were extracted from the selected transcripts. Three models are proposed based on the separate extraction of such feature sets, and a fourth model is based on an early fusion strategy of the proposed feature sets. All the models were optimized following a Leave-One-Out cross validation strategy. Accuracies of up to 81.7 % were achieved using the early fusion of the three feature sets. Furthermore, we found that, with a small set of grammar features, accuracy values of up to 72.8 % were obtained. The results show that such features are suitable to effectively classify AD patients and healthy controls.

scholarly journals Kynurenic Acid Electrochemical Immunosensor: Blood-Based Diagnosis of Alzheimer’s Disease

Biosensors ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 20
Author(s):  
Jose Marrugo-Ramírez ◽  
Montserrat Rodríguez-Núñez ◽  
M.-Pilar Marco ◽  
Mónica Mir ◽  
Josep Samitier
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Kynurenic Acid ◽  
Electrochemical Impedance ◽  
Neurodegenerative Disorder ◽  
Limit Of Detection ◽  
Electrochemical Immunosensor ◽  
Protective Function ◽  
Potential Biomarker ◽  
The Brain

Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by a functional deterioration of the brain. Currently, there are selected biomarkers for its diagnosis in cerebrospinal fluid. However, its extraction has several disadvantages for the patient. Therefore, there is an urgent need for a detection method using sensitive and selective blood-based biomarkers. Kynurenic acid (KYNA) is a potential biomarker candidate for this purpose. The alteration of the KYNA levels in blood has been related with inflammatory processes in the brain, produced as a protective function when neurons are damaged. This paper describes a novel electrochemical immunosensor for KYNA detection, based on successive functionalization multi-electrode array. The resultant sensor was characterized by cyclic voltammetry (CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). The proposed biosensor detects KYNA within a linear calibration range from 10 pM to 100 nM using CA and EIS, obtaining a limit of detection (LOD) of 16.9 pM and 37.6 pM in buffer, respectively, being the lowest reported LOD for this biomarker. Moreover, to assess our device closer to the real application, the developed immunosensor was also tested under human serum matrix, obtaining an LOD of 391.71 pM for CA and 278.8 pM for EIS with diluted serum.

scholarly journals CSF Biomarker Profiles in CNS Infection Associated with HSV and VZV Mimic Pattern in Alzheimer’s Disease.

2020 ◽  
Author(s):  
Makiko Shinomoto ◽  
Takashi Kasai ◽  
Harutsugu Tatebe ◽  
Fukiko Kitani-Morii ◽  
Takuma Ohmichi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Axonal Injury ◽  
Cns Infection ◽  
Mri Findings ◽  
Cns Infections ◽  
Potential Biomarker ◽  
Hospitalization Period ◽  
Significant Difference

Abstract Alzheimer’s disease (AD) is the most common cause of dementia. Although AD was initially considered to be a cell autonomous neurodegenerative disorder, marked neuroinflammation is observed in the brains of patients with AD, alongside Aβ and tau pathology. Based on genetic and molecular biological findings, central nervous system (CNS) inflammatory processes have been postulated to be involved in the etiopathogenesis of AD, in which activated microglia play a key role. This has also been supported by the epidemiological observation that CNS infections were associated with the development of AD, and in particular the relationship between herpetic virus and AD has been well-investigated. For example, the presence of anti-herpes simplex virus (HSV) antibody was associated with an elevated risk of developing AD [1]. Moreover, anti-herpetic medication was associated with a reduced risk of dementia in a population-based study [2]. Similar results were also observed in the case of varicella zoster virus (VZV) infections [3]. Taking into consideration the reports above, we hypothesized that the biomarker signature representing AD might be observed in patients with herpetic viral CNS infections as a prognostic biomarker of AD development. In the current study, we aimed to determine whether or not the biomarkers related to AD and neurodegeneration were changed in patients with CNS infection by HSV and VZV compared with controls. This study focused on CSF levels of Aβ1-42, Aβ1-40, total-tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) as molecules representing the AD signature; neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (p-NfH) as indicators of axonal injury; soluble triggering receptor expressed on myeloid cells 2 (sTREM2) as a potential biomarker for microglia activity; and glial fibrillary acidic protein (GFAP) as a biomarker for astrocytic damage. We also measured serum levels of NfL as a blood based biomarker for axonal injury. (For detailed methods, see Supplementary methods) The demographic characteristics, diagnosis, CSF profiles, results of viral detection, magnetic resonance imaging (MRI) findings, lowest score of the Glasgow coma scale (GCS) during the hospitalization period, and modified Rankin Scale (mRS) at discharge are summarized in Supplementary Table 1 and 2. There was no significant difference in age or sex among the HSV, VZV, and control groups.

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