scholarly journals A Comparative Study of the Detection of cAMP response element binding protein (CREB) in the Peripheral Blood of Alzheimer's Patients and the Healthy subjects as a Biomarker for the diagnosis of Alzheimer

Author(s):  
Ahmad Chitsaz ◽  
Masih Falahatian ◽  
Moneer Hadadian

Introduction: Alzheimer's disease is a neurodegenerative disease, which usually helps some biomarkers, such as amyloid proteins, to diagnose the disease. Therefore, the purpose of this study was to compare the expression of a protein binding protein to the adjuvant responder to circular adenosine monophosphate (CREB) in peripheral blood of patients to Alzheimer's and healthy elderly people as a biomarker for diagnosing Alzheimer. Materials and Methods: In this case-control study, 32 patients with Alzheimer's disease and 32 normal blood samples were taken. Using real time PCR, CREB expression was evaluated. Results: The mean CREB level in the case group was 0.89 ± 0.30 and in the control group was 1.01 ± 0.03. The mean of BDNF level in the case group was significantly higher than the control group (P <0.001). There was no significant relationship between the level of CREB with age, sex, MMSE score and Cornell scale for depression in dementia (P> 0.05). Conclusion: Reducing CREB levels in people with Alzheimer's disease can be a factor in diagnosis in comparison to healthy people.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Luis Jáñez-Escalada ◽  
Lucía Jáñez-García ◽  
Elena Salobrar-García ◽  
Alejandro Santos-Mayo ◽  
Rosa de Hoz ◽  
...  

Abstract The retina is an attractive source of biomarkers since it shares many features with the brain. Thickness differences in 10 retinal layers between 19 patients with mild Alzheimer’s disease (AD) and a control group of 24 volunteers were investigated. Retinal layers were automatically segmented and their thickness at each scanned point was measured, corrected for tilt and spatially normalized. When the mean thickness of entire layers was compared between patients and controls, only the outer segment layer of patients showed statistically significant thinning. However, when the layers were compared point-by point, patients showed statistically significant thinning in irregular regions of total retina and nerve fiber, ganglion cell, inner plexiform, inner nuclear and outer segment layers. Our method, based on random field theory, provides a precise delimitation of regions where total retina and each of its layers show a statistically significant thinning in AD patients. All layers, except inner nuclear and outer segments, showed thickened regions. New analytic methods have shown that thinned regions are interspersed with thickened ones in all layers, except inner nuclear and outer segments. Across different layers we found a statistically significant trend of the thinned regions to overlap and of the thickened ones to avoid overlapping.


2008 ◽  
Vol 66 (3b) ◽  
pp. 619-624 ◽  
Author(s):  
Juliana Nery de Souza-Talarico ◽  
Paulo Caramelli ◽  
Ricardo Nitrini ◽  
Eliane Corrêa Chaves

BACKGROUND: Subjects with Alzheimer's disease (AD) have elevated cortisol levels as a result of hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Acute administration of hydrocortisone has been associated with working memory (WM) performance in young adults. OBJECTIVE: To investigate whether cortisol levels are associated with WM performance in subjects with AD. METHOD: Eighty subjects were included, comprising 40 patients with mild AD and 40 healthy elderly controls. WM was assessed using the Digit Span Backward test (DSB). Saliva samples were collected to determine cortisol levels. RESULTS: AD subjects had poorer performance on the DSB than controls (p=0.002) and also presented higher levels of cortisol than control group (p=0.04). No significant correlation was observed between the DSB and cortisol levels in both groups (r= -0.29). CONCLUSION: In this study, elevated cortisol levels were not associated with poorer WM performance in patients with AD or in healthy elderly subjects.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Chenyu Xia ◽  
Qiang Ma

Objective. To analyze the levels of amyloid β-protein and P181 in peripheral blood of patients with Alzheimer’s disease combined with Helicobacter pylori infection and their clinical significance. Method. From January 2019 to June 2020, 59 patients were enrolled in this experiment including the AD group with 27 patients and the normal control group with 32 patients. The patients were divided into two groups: Alzheimer’s disease (AD) group ( n = 27 ) and control group ( n = 32 ), collecting the general data of patients, analyzing the diagnostic specificity and sensitivity of serum p-tau181 and Aβ42 and their influence on prognosis, and comparing the serum Aβ42 and p-tau181 concentrations for different HP infection degrees. Result. Single diagnostic sensitivity of Aβ42, p-tau181, and Aβ42 combined p-tau181 was 0.863, 0.854, and 0.972, respectively, and their specificity was 0.048, 0.206, and 0.305, respectively. Compared with the single diagnosis of serum Aβ42 and p-tau181, the combined diagnosis has higher sensitivity and specificity ( P < 0.05 ); age, years of education, serum Aβ42, and p-tau181 are factors affecting the prognosis of patients with Alzheimer’s disease combined with Helicobacter pylori infection; the concentration of Aβ42 in the control group was higher than that in the AD group, there was a statistical difference in the Aβ42 concentration between the two groups ( P < 0.05 ), and there was no statistical difference in the concentration of p-tau181 between the two groups ( P > 0.05 ); the HP positive infection rate of the AD group and the control group was 63.0% and 35.7%, respectively. The HP negative infection rate of the AD group and the control group was 37.0% and 64.3%, respectively. Compared with the control group, the positive rate of HP in the AD group was higher, and the difference was statistically significant ( P < 0.05 ); compared with HP-negative patients, HP-positive patients had a higher Aβ42 concentration, and the difference was statistically significant ( P < 0.05 ). The concentration of p-tau181 in the two groups was not statistically significant ( P > 0.05 ); Aβ42 gradually increases with increasing HP infection degree, and there are significant differences in serum Aβ42 levels between different degrees of infection. However, the level of serum p-tau181 does not change significantly with the increase of infection. Conclusion. There are significant alterations in the expression levels of Aβ42 and p-tau181 in peripheral blood of AD patients, and the levels of Aβ42 are related to HP infection; Aβ42 and p-tau181 are potential biomarkers for AD diagnosis and treatment.


2021 ◽  
Vol 18 ◽  
Author(s):  
Vivek Kumar Sharma ◽  
Thakur Gurjeet Singh

: Alzheimer’s disease (AD) is a persistent neuropathological stipulation manifested in the form of neuronal/synapse demise, the formation of senile plaques, hyperphosphorylated tau tangles, neuroinflammation, and apoptotic cell death. The absence of a therapeutic breakthrough for AD has continued the quest to find a suitable intervention. Apart from various candidates, the cyclic AMP-protein kinase A-cAMP response element-binding protein (cAMP/PKA/CREB) pathway is the most sought-after drug target AD as the bulk of quality literature documents that there is downregulation of cAMP signaling and CREB mediated transcriptional cascade in AD. cAMP signaling is evolutionarily conserved and can be found in all species. cAMP response element-binding protein (CREB) is a ubiquitous and integrally articulated transcription aspect that regulates neuronal growth, neuronal differentiation/proliferation, synaptic plasticity, neurogenesis, maturation of neurons, spatial memory, long-term memory formation as well as ensures neuronal survival. CREB is a central part of the molecular machinery that has a role in transforming short-term memory to long-term. Besides AD, impairment of CREB signaling has been well documented in addiction, Parkinsonism, schizophrenia, Huntington’s disease, hypoxia, preconditioning effects, ischemia, alcoholism, anxiety, and depression. The current work highlights the role and influence of CREB mediated transcriptional signaling on major pathological markers of AD (amyloid β, neuronal loss, inflammation, apoptosis, etc.). The present work justifies the continuous efforts being made to explore the multidimensional role of CREB and related downstream signaling pathways in cognitive deficits and neurodegenerative complications in general and AD particularly. Moreover, it is reaffirmed that cyclic nucleotide signaling may have vast potential to treat neurodegenerative complications like AD.


2021 ◽  
Vol 79 (4) ◽  
pp. 1509-1515
Author(s):  
Alberto Castagna ◽  
Andrea Fabbo ◽  
Ciro Manzo ◽  
Roberto Lacava ◽  
Carmen Ruberto ◽  
...  

Background: Background: Citicoline has been proven to have beneficial effects in patients with cognitive impairment. In previous studies, combined treatment with memantine and acetylcholinesterase inhibitors (AChEIs) maintained cognitive function in patients with Alzheimer’s disease (AD) better than memantine or AChEIs alone. Objective: To evaluate the effectiveness and safety of a combination therapy of oral citicoline, memantine, and an AChEI in AD when compared with memantine and an AChEI without citicoline. Methods: This was a retrospective multi-centric case-control study, conducted in Italian Centers for Cognitive Impairment and Dementia. Overall, 170 patients were recruited (34.11%of men, mean age 76,81±4.93 years): 48.8%treated with memantine and donepezil; 48.2%with memantine and rivastigmine; 2.9%with memantine and galantamine. 89 patients (control-group) were treated with memantine and an AChEI, whereas 81 patients (case-group) were treated with oral citicoline 1000 mg/day added to memantine and an AChEI given orally. Cognitive functions, activities of daily living, instrumental activities of daily living, comorbidities, mood and behavioral disturbances were assessed at baseline, month 6, and month 12. Results: In the case group, MMSE score had a statistically significant increasing trend between T0 and T2 (14.88±2.95 versus 15.09±3.00; p = 0.040), whereas in the control group, MMSE score showed a statistically significant decrease trend (14.37±2.63 versus 14.03±2.92 p = 0.024). Conclusion: In older patients with AD, a triple therapy with citicoline, memantine, and AChEI was more effective than memantine and AChEI without citicoline in maintaining the MMSE total score after 12 months.


2021 ◽  
Vol 18 ◽  
Author(s):  
María del Carmen Pérez-Sánchez ◽  
María González-Nosti ◽  
Fernando Cuetos ◽  
Carmen Martínez ◽  
Marta Álvarez-Cañizo

Background: Reading fluency is essential for our functioning in the literate society in which we live. Reading expressiveness or prosody, along with speed and accuracy, are considered key aspects of fluent reading. Prosodic patterns may vary, not being the same in children learning to read as in adulthood. But little is known about the prosodic characteristics and reading fluency of people with neurodegenerative diseases that causes language impairment and reading difficul- ties, such as Alzheimer’s disease (AD). Objective: The aim of this work was to study reading fluency in AD, considering reading speed, ac- curacy and reading prosody. Method: The participants were 20 healthy elderly Spanish adults, and 20 AD patients, aged 64-88 years. An experimental text was designed, that included declarative, exclamatory, and interrogative sentences, words with different stresses and low-frequency words. The reading of the participants was recorded and analyzed using Praat software. Results: The AD group showed significantly longer reading duration, both at the syllable level and at the word and sentence level. These patients also committed more pauses between words, which were also longer, and more reading errors. The control group showed a variation of the syllabic F0 in the three types of sentences, while these variations only appeared in declarative ones in the AD group. Conclusion: The pauses, along with the slight pitch variations and the longer reading times and er- rors committed, compromise the reading fluency of people with AD. Assessment of this reading feature could be interesting as a possible diagnostic marker for the disease.


1994 ◽  
Vol 7 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Edward P. Feher ◽  
Glenn J. Larrabee ◽  
Abraham Sudilovsky ◽  
Thomas H. Crook

We investigated memory self-report in Alzheimer's disease (AD) and age-assodated memory impairment (AAMI). AD and AAMI patients and healthy elderly subjects were administered a self-report memory questionnaire, memory tests, a family-rated memory questionnaire, and a depression scale. The AD group reported worse memory than the control group, but many individual AD subjects reported normal memory. This finding confirms clinical observations that unawareness of memory loss is common in AD but variable across patients. Multiple regression analysis revealed that worse memory self-ratings were associated with greater dementia severity and higher depression scores. In the AAMI group, memory self-ratings were predicted by family ratings of memory ability but not by memory test scores. There was a nonsignificant trend for depression scores to predict memory self-ratings. Finally, level of self-repor, ted memory ability did not differ for AD and AAMI, contradicting clinical lore that memory complaint is a useful diagnostic indicator.


Author(s):  
Nasim Sattari ◽  
◽  
Fariborz Faeghi ◽  
Babak Shekarchi ◽  
Mohammad Hossein Heidari ◽  
...  

Purpose: In this study, the main goal was to determine the correlation between the thickness of cerebral cortex and the severity of cognitive disorder in Alzheimer's disease Materials and method: Twenty patients diagnosed with Alzheimer’s disease with mean age of 72.95 year(14 women and 6 men) and Ten Cognitively normal (CN) subjects with mean age of 70.50 year( 7 women and 3 men) were included to the study. Of the AD patient and CN subjects, 70% were female and 30% were male. All individual underwent 1.5 T MRI. The MR scanning protocol included 3D MPRAGE (3D-T1W) sequence. All images were analyzed using Freesurfer v5.3 and then calculated the brain cortical thickness in 7 cortex( Inferior temporal, Middle temporal, Superior temporal, parahippocamp, parstriangularis, rostralmiddle frontal, Superior frontal). Result: The Analysis of covariance (ANCOVA) was conducted to compare the means of each region between the patient whilst control group. There was a significant difference in mean of cortical thickness in all regions. In all cases the mean of cortical thickness in CN subjects were greater than AD patients. However, the mean of Parstriangularis left hand in CN subjects was not significantly greater than the one in AD patients. The receiver operating characteristic system (ROC) was designed to evaluate the predictive power of the patient and the healthy person. We have selected a thousand cut-off points from 1.5 to 3.5mm for cortical thickness. When the cut-off points were interval (2.276878, 2.299680) millimeter in left hemisphere, the Youden’s index was maximized. The sensitivity and specificity in this case were 80%. Also when the cut-off points were within the range (2.263278, 2.282278) mm in right hemisphere, the sensitivity and specificity were 90% and 80%, respectively. Conclusion: This study demonstrates the importance of quantify the cortical thickness changes in early diagnosis of Alzheimer’s disease. In addition, examining the pattern of changes and the quantifying the reduction in the thickness of the cortex is an important tool for displaying the local and global atrophy of the brain. Also, this pattern can be used as an alternative marker for the diagnosis of dementia. Finally, to the best of our knowledge, our study is the first one to report finding on the range of cortical thickness that would help clinician to have better differential diagnose and also in this study have checked the possibility of early diagnosis of the disease.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Helena Sophia Gleerup ◽  
Steen Gregers Hasselbalch ◽  
Anja Hviid Simonsen

Background. The histopathological changes of Alzheimer’s disease (AD) are detectable decades prior to its clinical expression. However, there is a need for an early, inexpensive, noninvasive diagnostic biomarker to detect specific Alzheimer pathology. Recently developed neuroimaging biomarkers show promising results, but these methods are expensive and cause radiation. Furthermore, the analysis of cerebrospinal fluid (CSF) biomarkers requires an invasive lumbar puncture. Saliva is an easily obtained body fluid, and a stable saliva biomarker would therefore be a promising candidate for a future method for diagnosing AD. The purpose of this systematic review was to investigate studies of biomarkers in saliva samples for the diagnosis of AD. Methods. The included articles were identified through a literature search in PubMed and Google Scholar for all articles until November 1st, 2018, and furthermore, all reference lists of included articles were reviewed by hand. We included articles written in English investigating saliva from patients with AD and a control group. Results. A total of 65 studies were identified, whereof 16 studies met the inclusion criteria and were included in the systematic review. A plethora of different biomarkers were investigated, and ten out of the sixteen studies showed a statistical significance in biomarkers between patients with AD and healthy, elderly controls, among these biomarkers for specific AD pathology (amyloid beta 1-42 (Aβ42) and tau). Conclusion. Aβ42 and tau seem to be worthy candidates for future salivary biomarkers for AD, but other biomarkers such as lactoferrin and selected metabolites also have potential. More studies must be carried out with larger sample sizes and a standardization of the sampling and processing method. Factors such as diurnal variation, AD patients’ decreased ability of oral self-care, and salivary flowrates must be taken into consideration.


2021 ◽  
Vol 8 (06) ◽  
pp. 5498-5507
Author(s):  
Huseyin Fatih Gul ◽  
Caner Yildirim ◽  
Can Emre Erdogan ◽  
Ozlem Gul ◽  
Nazlı Koc

The roles of novel peptides such as peroxisome proliferator-activated receptor gamma coactivator 1- alpha (PGC1-α), irisin, brain-derived neurotrophic factor (BDNF), galanin and alarin in Alzheimer's disease (AD) are not fully known. It was aimed to plasma levels of the novel peptides that may affect the pathophysiology of AD were examined. This study was conducted as a cross-sectional. The study consisted of two groups, including 45 newly diagnosed individuals with AD and 45 healthy individuals. The peptide levels in plasma samples collected from the groups were measured by the ELISA method. The mean plasma peptide levels and age differences, between the groups, and the correlations between them were analyzed by the statistically. The means ages of both groups were over 65 years old. When plasma PGC1-α, irisin, BDNF, galanin, and alarin levels between the groups were examined, decreases were found in the group with AD (3.56±0.79ng/mL, 16.33±4.07ng/mL, 3.36±1.47ng/mL, 13.93±4.24ng/L, 31.99±11.89pg/mL, respectively) compared to the control group (4.23±1.31ng/mL, 22.19±9.61ng/mL, 4.58±2.10ng/mL, 14.4±9.01ng/L, 54.93±15.80pg/mL, respectively). In the negative correlations observed between age and plasma peptide levels. Significant positive correlations were observed between plasma PGC1-α levels and irisin, alarin, and BDNF, and the significant positive correlations were also observed between plasma BDNF levels and irisin and alarin. As far as we know, the study is the first report in which the peptides mentioned in AD were examined together. We consider that more detailed studies are needed to shed light on the roles and mechanisms of these peptides in AD.


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