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.

scholarly journals Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: an elusive quest

2019 ◽  
Vol 90 (7) ◽  
pp. 740-746 ◽  
Author(s):  
Martha S Foiani ◽  
Claudia Cicognola ◽  
Natalia Ermann ◽  
Ione O C Woollacott ◽  
Carolin Heller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Dementia ◽  
Neurodegenerative Disorder ◽  
The Novel ◽  
Tau Pathology ◽  
Total Tau ◽  
Significant Difference ◽  
T Tau

BackgroundFrontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer’s disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD.Methods86 participants were included: 66 with a clinical diagnosis within the FTD spectrum and 20 healthy controls. Immunoassays targeting tau fragments N-123, N-mid-region, N-224 and X-368, as well as a non-phosphorylated form of tau were measured in CSF, along with total-tau (T-tau) and phospho-tau (P-tau(181)). Patients with FTD were grouped based on their Aβ42 level into those likely to have underlying Alzheimer’s disease (AD) pathology (n=21) and those with likely frontotemporal lobar degeneration (FTLD) pathology (n=45). The FTLD group was then subgrouped based on their underlying clinical and genetic diagnoses into those with likely tau (n=7) or TDP-43 (n=18) pathology.ResultsSignificantly higher concentrations of tau N-mid-region, tau N-224 and non-phosphorylated tau were seen in both the AD group and FTLD group compared with controls. However, none of the novel tau species showed a significant difference between the AD and FTLD groups, nor between the TDP-43 and tau pathology groups. In a subanalysis, normalising for total-tau, none of the novel tau species provided a higher sensitivity and specificity to distinguish between tau and TDP-43 pathology than P-tau(181)/T-tau, which itself only had a sensitivity of 61.1% and specificity of 85.7% with a cut-off of <0.109.ConclusionsDespite investigating multiple novel CSF tau fragments, none show promise as an FTD biomarker and so the quest for in vivo markers of FTLD-tau pathology continues.

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 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 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 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 ◽  
Disease Severity ◽  
Amyloid Β ◽  
Cns Infection ◽  
Control Group ◽  
Neurofilament Light Chain ◽  
Cns Infections ◽  
Csf Biomarker ◽  
T Tau

Abstract Background: Central nervous system (CNS) infections have been reported to have a certain etiological relevance to Alzheimer’s disease (AD). In particular, herpes simplex virus (HSV) and varicella zoster virus (VZV) infections has been reported as risk factors for AD. The aim of this study was to determine whether or not AD-related biomarkers were changed in patients with HSV or VZV CNS infections.Methods: Nine patients with HSV infection of the CNS, eight patients with VZV complicated by CNS involvement, and eighteen age-matched controls were enrolled. Amyloid β (Aβ)1-42, Aβ1-40, total-tau (t-tau), tau phosphorylated at threonine 181 (p-tau), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (p-NfH), glial fibrillary acidic protein (GFAP), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in were measured in cerebrospinal fluid (CSF), and NfL in serum.Results: Compared with the control group, CSF Aβ1-42, Aβ1-40, and the Aβ1-42/ Aβ1-40 ratio were significantly decreased, and CSF t-tau, p-tau, sTREM2, and GFAP were significantly increased in the HSV and VZV combined group, in which biomarker changes were similar to those reported in AD. CSF NfL levels measured on admission were significantly correlated with the disease severity and a poor outcome after age adjustment. Serum NfL on admission was also associated with disease severity after age adjustment.Conclusions: The fact that the biomarker profile in patients with CNS HSV and VZV infections mimicked that in AD patients should be paid attention to as a potential confounding factor in CSF biomarker-based diagnosis of AD, and it suggests an etiological similarity between herpetic virus infection and AD. The CSF NfL concentration on admission may be useful as a predictive marker of severity and prognosis in patients with CNS HSV and VZV infections.

scholarly journals Association of MS4A6A, CD33, and TREM2 gene polymorphisms with the late-onset Alzheimer’s disease

Bioimpacts ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 219-225 ◽  
Author(s):  
Elham Mehdizadeh ◽  
Mohammad Khalaj-Kondori ◽  
Zeinab Shaghaghi-Tarakdari ◽  
Saeed Sadigh-Eteghad ◽  
Mahnaz Talebi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphisms ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Salting Out ◽  
Age And Gender ◽  
Blood Samples ◽  
Significant Difference ◽  
And Gender

Introduction: Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder, causes structural and functional brain disruption. MS4A6A, TREM2, and CD33 gene polymorphisms loci have been found to be associated with the pathobiology of late-onset AD (LOAD). In the present study, we tested the hypothesis of association of LOAD with rs983392, rs75932628, and rs3865444 polymorphisms in MS4A6A, TREM2, CD33 genes, respectively.Methods: In the present study, 113 LOAD patients and 100 healthy unrelated age- and gender-matched controls were selected. DNA was extracted from blood samples by the salting-out method and the genotyping was performed by RFLP-PCR. Electrophoresis was carried out on agarose gel. Sequencing was thereafter utilized for the confirmation of the results. Results: Only CD33 rs3865444 polymorphism revealed a significant difference in the genotypic frequencies of GG (P = 0.001) and GT (P = 0.001), and allelic frequencies of G (P = 0.033) and T (P = 0.03) between LOAD patients and controls. Conclusion: The evidence from the present study suggests that T allele of CD33 rs3865444 polymorphism is associated with LOAD in the studied Iranian population.

scholarly journals Monoclonal antibodies in the treatment of Alzheimer’s disease: a literature review

2021 ◽  
Author(s):  
Pedro Henrique Carvalho Furtado de Mendonça ◽  
Fernanda Rabello Detoni ◽  
Letícia Silva Brandão dos Santos ◽  
Talita Cardoso Gomes ◽  
Ivan Magalhães Viana
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Monoclonal Antibodies ◽  
Neurodegenerative Disorder ◽  
Controlled Trial ◽  
Test Group ◽  
Pubmed Database ◽  
Significant Difference ◽  
Collateral Effects ◽  
Aβ Aggregation

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder, whose treatment is limited to drugs that offer comfort to the patient. Immunotherapy with monoclonal antibodies (mAbs) has been the subject of a study with the promise of reversing cognitive deficits. In this scenario, we conducted a systematic review to elucidate aspects about the effectiveness of such treatment. Objectives: Analyze the prognostic of patients with AD through immunotherapy using anti-amilody mAbs. Methods: It was used the PubMed database using the descriptors: “Amyloid beta-Peptides AND Alzheimer disease AND Immunotherapy”. Filters: clinical trial, randomized controlled trial. 6 articles from 2015 to 2021 were selected. Inclusion criteria: (1) mAbs as treatment for AD; (2) Analyze the prognostic. Results: The immunotherapy with bapineuzumab and solanezumab didn’t showed no statistically significant difference between the groups of bapineuzumab 0,5 mg / kg (p = 0,979) and placebo (p = 0,973) and a change of 6.65 in the solanezumab group and 7.44 in the placebo group (difference, −0.80; P = 0 , 10). However, subcutaneous treatment of bapineuzumab exhibited fewer abnormalities of images related to amyloid with edema or effusion (AIRA), so, better tolerated compared to intravenous treatment. In the study with the ABvac40 vaccine, about 92% of the individuals in the test group developed specific anti-Aβ 40 antibodies. Conclusion: Bapineuzumab and solanezumab didn’t achieve significant results in the reduction of cognitive decline, however bapineuzumab enabled the prevention of Aβ aggregation. However, the use of mAbs can trigger collateral effects, requiring an individual analysis.

scholarly journals EEG Biomarker for Alzheimer’s Disease

2020 ◽  
Author(s):  
Demet Ilhan Algin ◽  
Demet Ozbabalık Adapinar ◽  
Oguz Osman Erdinc
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Low Cost ◽  
Cost Effective ◽  
Event Related Potential ◽  
Cortical Atrophy ◽  
Mri Findings ◽  
Magnetic Resonance Imaging Mri ◽  
Electroencephalogram Eeg

Alzheimer’s disease (AD) is a neurodegenerative disorder that accounts for nearly 70% of the more than 50 million dementia cases estimated worldwide. There is no cure for AD. Currently, AD diagnosis is carried out using neuropsychological tests, neuroimaging scans, and laboratory tests. In the early stages of AD, brain computed tomography (CT) and magnetic resonance imaging (MRI) findings may be normal, but in late periods, diffuse cortical atrophy can be detected more prominently in the temporal and frontal regions. Electroencephalogram (EEG) is a test that records the electrical signals of the brain by using electrodes that directly reflects cortical neuronal functioning. In addition, EEG is noninvasive and widely available at low cost, has high resolution, and provides access to neuronal signals, unlike functional MR or PET which indirectly detects metabolic signals. Accurate, specific, and cost-effective biomarkers are needed to track the early diagnosis, progression, and treatment response of AD. The findings of EEG in AD are now identified as biomarkers. In this chapter, we reviewed studies that used EEG or event-related potential (ERP) indices as a biomarker of AD.

scholarly journals Increased astrocyte representation in the hippocampus of 5xFAD mice

2021 ◽  
Vol 72 (2) ◽  
pp. 5-10
Author(s):  
Violeta Jovanović ◽  
Jelica Despotović ◽  
Mario Balo ◽  
Ivan Zaletel ◽  
Sanja Despotović ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Amyloid Plaques ◽  
Control Group ◽  
Significant Difference ◽  
5Xfad Mice ◽  
And Control

Introduction: Alzheimer's disease is the most common neurodegenerative disorder, characterized by the formation of amyloid plaques and the neurofibrillary tangles in the brain of an ill person, leading to neuronal damage and loss. Activation of astrocytes and astrogliosis occurs along with this process. Due to ethical limitations in working with human tissue, numerous transgenic animal models have been developed to study the pathogenesis of these processes. Early Ab deposition is observed in the cortex and the hippocampus. Aim: This study aimed to determine the difference in the presence of GFAP positive cells in the hippocampus between transgenic 5xFAD mice aged 36 weeks and their corresponding controls. Material and Methods: The 5xFAD mice model of Alzheimer's disease was used, characterized by early formation of amyloid plaques but without the presence of neurofibrillar tangles. Transgenic and control animals were sacrificed at 36 weeks of age. The visualization of GFAP-positive cells in the hippocampus of their brains was done by using immunohistochemistry and antibody for glial fibrillary acidic protein - GFAP, the major marker of astrocytes. Quantification of immuno-reactivity was done by using the Icy software system. Results: There was a statistically significant difference in the expression of GFAP in the dentate gyrus and the granular zone of the hippocampus between the transgenic and control group at 36 weeks of age, while the significant change in the CA1-3 regions was not observed between investigated groups. Conclusion: Obtained results confirm the involvement of astrogliosis in the pathophysiology of Alzheimer's disease and indicate an earlier occurrence of astrogliosis in the dentate gyrus and granular zone, in relation to other regions of the hippocampus, in the 36-week-old 5xFAD mice.

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