Identification of Serum Biomarkers in Patients with Alzheimer’s Disease by 2D-DIGE Proteomics

Gerontology ◽  
2022 ◽  
pp. 1-13
Author(s):  
Xuezhi Zhang ◽  
Wenwen Yu ◽  
Xuelei Cao ◽  
Yongbin Wang ◽  
Chao Zhu ◽  
...  

<b><i>Aim:</i></b> The aim of this study is to identify potential serum biomarkers of Alzheimer’s disease (AD) for early diagnosis and to evaluate these markers on a large cohort. <b><i>Methods:</i></b> We performed two-dimensional difference gel electrophoresis to compare the serum of AD patients and normal controls. Western blot or enzyme-linked immunosorbent assay (ELISA) was used to identify the expression levels of proteins. <b><i>Results:</i></b> In this study, a total of 13 differentially expressed proteins were identified. Among them, 2 proteins (inter-alpha-trypsin inhibitor heavy chain H4 [ITI-H4], Apolipoprotein A-IV) were validated by Western blot and 4 proteins (Cofilin 2, Tetranectin, Zinc-alpha-2-glycoprotein [AZGP1], Alpha-1-microglobulin/bikunin precursor [AMBP]) were validated by ELISA, respectively. Western blot results showed that the full size of the ITI-H4 protein was increased, while a fragment of ITI-H4 was decreased in AD patients. In contrast, 1 fragment of Apo A-IV was mainly found in control group and rare to be detected in AD patients. On the other hand, ELISA results showed that Cofilin 2, Tetranectin, AZGP1, and AMBP were significantly increased in AD patients, and Cofilin 2 is strongly correlated with the Mini-Mental State Examination scores of the AD patients. Serum Cofilin 2 was unchanged in Parkinson disease patients as compared to the control group, indicating a specific correlation of serum Cofilin 2 with AD. Moreover, Cofilin 2 was increased in both the serum and brain tissue in the APP/PS1 transgenic mice. <b><i>Conclusion:</i></b> Our study identified several potential serum biomarkers of AD, including: ITI-H4, ApoA-IV, Cofilin 2, Tetranectin, AZGP1, and AMBP. Cofilin 2 was upregulated in different AD animal models and might play important roles in AD pathology.

2011 ◽  
Vol 69 (2b) ◽  
pp. 297-303 ◽  
Author(s):  
L C Fonseca ◽  
G M A S Tedrus ◽  
L R Prandi ◽  
A C A Andrade

OBJECTIVE: To evaluate the contribution of quantitative electroencephalographic (qEEG) analyses in the diagnosis of Alzheimer's disease (AD). METHOD: Thirty-five patients from the Neurology Outpatients Clinic of PUC-Campinas, diagnosed with AD according to the NINCDS/ADRDA were evaluated, and compared with a control group consisting of 30 individuals with no cognitive deficit. The procedures consisted of clinical-neurological, cognitive and behavioral analyses and the qEEG (absolute power and coherence). RESULTS: The AD group presented greater absolute power values in the delta and theta bands, greater theta/alpha indices and less frontal alpha and beta coherence. Logistic multiple regression models were constructed and those only showing variations in the qEEG (frontal alpha coherence and left frontal absolute theta power) showed an accuracy classification (72.3%) below that obtained in the mini-mental state examination (93%). CONCLUSION: The study of coherence and power in the qEEG showed a relatively limited accuracy with respect to its application in routine clinical practice.


2013 ◽  
Vol 25 (10) ◽  
pp. 1679-1685 ◽  
Author(s):  
Maysa Luchesi Cera ◽  
Karin Zazo Ortiz ◽  
Paulo Henrique Ferreira Bertolucci ◽  
Thaís Soares Cianciarullo Minett

ABSTRACTBackground:Alzheimer's disease (AD) affects not only memory but also other cognitive functions, such as orientation, language, praxis, attention, visual perception, or executive function. Most studies on oral communication in AD focus on aphasia; however, speech and orofacial apraxias are also present in these patients. The aim of this study was to investigate the presence of speech and orofacial apraxias in patients with AD with the hypothesis that apraxia severity is strongly correlated with disease severity.Methods:Ninety participants in different stages of AD (mild, moderate, and severe) underwent the following assessments: Clinical Dementia Rating, Mini-Mental State Examination, Lawton Instrumental Activities of Daily Living, a specific speech and orofacial praxis assessment, and the oral agility subtest of the Boston diagnostic aphasia examination.Results:The mean age was 80.2±7.2 years and 73% were women. Patients with AD had significantly lower scores than normal controls for speech praxis (mean difference=−2.9, 95% confidence interval (CI)=−3.3 to −2.4) and orofacial praxis (mean difference=−4.9, 95% CI=−5.4 to −4.3). Dementia severity was significantly associated with orofacial apraxia severity (moderate AD: β=−19.63, p=0.011; and severe AD: β=−51.68, p < 0.001) and speech apraxia severity (moderate AD: β=7.07, p = 0.001; and severe AD: β= 8.16, p < 0.001).Conclusion:Speech and orofacial apraxias were evident in patients with AD and became more pronounced with disease progression.


2012 ◽  
Vol 153 (12) ◽  
pp. 461-466 ◽  
Author(s):  
Magdolna Pákáski ◽  
Gergely Drótos ◽  
Zoltán Janka ◽  
János Kálmán

The cognitive subscale of the Alzheimer’s Disease Assessment Scale is the most widely used test in the diagnostic and research work of Alzheimer’s disease. Aims: The aim of this study was to validate and investigate reliability of the Hungarian version of the Alzheimer’s Disease Assessment Scale in patients with Alzheimer’s disease and healthy control subjects. Methods: syxty-six patients with mild and moderate Alzheimer’s disease and 47 non-demented control subjects were recruited for the study. The cognitive status was established by the Hungarian version of the Alzheimer’s Disease Assessment Scale and Mini Mental State Examination. Discriminative validity, the relation between age and education and Alzheimer’s Disease Assessment Scale, and the sensitivity and specificity of the test were determined. Results: Both the Mini Mental State Examination and the Alzheimer’s Disease Assessment Scale had significant potential in differentiating between patients with mild and moderate stages of Alzheimer’s disease and control subjects. A very strong negative correlation was established between the scores of the Mini Mental State Examination and the Alzheimer’s Disease Assessment Scale in the Alzheimer’s disease group. The Alzheimer’s Disease Assessment Scale showed slightly negative relationship between education and cognitive performance, whereas a positive correlation between age and Alzheimer’s Disease Assessment Scale scores was detected only in the control group. According to the analysis of the ROC curve, the values of sensitivity and specificity of the Alzheimer’s Disease Assessment Scale were high. Conclusions: The Hungarian version of the Alzheimer’s Disease Assessment Scale was found to be highly reliable and valid and, therefore, the application of this scale can be recommended for the establishment of the clinical stage and follow-up of patients with Alzheimer’s disease. However, the current Hungarian version of the Alzheimer’s Disease Assessment Scale is not sufficient; the list of words and linguistic elements should be selected according to the Hungarian standard in the future. Orv. Hetil., 2012, 153, 461–466.


2014 ◽  
Vol 72 (4) ◽  
pp. 273-277 ◽  
Author(s):  
José Roberto Wajman ◽  
Fabricio Ferreira de Oliveira ◽  
Rodrigo Rizek Schultz ◽  
Sheilla de Medeiros Correia Marin ◽  
Paulo Henrique Ferreira Bertolucci

Cognitive assessment in advanced stages of Alzheimer’s disease (AD) is limited by the imprecision of most instruments. Objective: To determine objective cognitive responses in moderate and severe AD patients by way of the Severe Mini-Mental State Examination (SMMSE), and to correlate performances with Mini-Mental State Examination (MMSE) scores. Method: Consecutive outpatients in moderate and severe stages of AD (Clinical Dementia Rating 2.0 or 3.0) were evaluated and compared according to MMSE and SMMSE scores. Results: Overall 400 patients were included, 67.5% females, mean age 76.6±6.7 years-old. There was no significant impact of age or gender over MMSE or SMMSE scores. Mean schooling was 4.4±2.5 years, impacting SMMSE scores (p=0.008). Scores on MMSE and SMMSE were significantly correlated (F-ratio=690.6325, p<0.0001). Conclusion: The SMMSE is influenced by schooling, but not by age or gender, and is an accurate test for assessment of moderate and severe AD.


2021 ◽  
Vol 9 (C) ◽  
pp. 5-9
Author(s):  
Anak Agung Ayu Putri Laksmidewi ◽  
Chiquita Putri Vania Rau

BACKGROUND: Dementia is one of the leading causes of disability and dependence in elderly worldwide. Epidemiological statistics indicate that data show that at about 60–80%, Alzheimer’s is the most common type of dementia. Alzheimer’s is also the third-most prominent cause of death in elderly. CASE REPORT: A 72-years-old male patient, complained by the family often forgets about things that have just been done for 3 years ago. According to the family, patient also often discussing the same things repeatedly. Patients tend not to have the initiative to start his daily activities. The family admitted that patient also became often angry and felt suspicious for the last 2 years. From the mini mental state examination showed disturbances in time orientation and recall; from Montreal Cognitive Assessment Ina found disturbances in visuospatial, fluency, abstraction, delayed memory, and time orientation; accompanied by activities of daily living (ADL) and instrumental ADL disorders. Patient also performed a molecular examination of the apolipoprotein E (APOE) genotype and the genotype E3/E4 was detected. CONCLUSION: The function of the APOE gene, in particular APOE4, is the most emphasized genetic relationship in late onset Alzheimer’s disease. It is proposed that blocking the action of APOE4 can delay or stop Alzheimer’s disease progression.


2020 ◽  
Author(s):  
Nira Cedres ◽  
Urban Ekman ◽  
Konstantinos Poulakis ◽  
Sara Shams ◽  
Lena Cavallin ◽  
...  

Abstract BACKGROUND We investigated the association between atrophy subtypes of Alzheimer’s disease (AD), the ATN classification scheme, and key demographic and clinical factors, in two cohorts with different source characteristics (a highly selective research-oriented cohort, ADNI; and a naturalistic heterogeneous clinically-oriented cohort, Karolinska Imaging Dementia Study (KIDS). METHODS A total of 382 AD patients were included. Factorial analysis of mixed data was used to investigate associations between AD subtype based on brain atrophy patterns, ATN profiles based on cerebrospinal fluid biomarkers, and age, sex, Mini Mental State Examination (MMSE), cerebrovascular disease (CVD) (burden of white matter signal abnormalities, WMSA), and APOE genotype. RESULTS Older patients with high WMSA burden, belonging to the typical AD subtype, and showing A + T + N + or A + T + N- profiles clustered together and were mainly from ADNI. Younger patients with low WMSA burden, limbic-predominant or minimal atrophy AD subtypes, and A + T-N- or A + T-N + profiles, clustered together and were mainly from KIDS. APOE ε4 carriers more frequently showed the A + T-N- and A + T + N- profiles. CONCLUSIONS Our findings align with the recent framework for biological subtypes of AD: the combination of risk factors, protective factors, and brain pathologies determines belonging of AD patients to distinct subtypes.


1990 ◽  
Vol 47 (1) ◽  
pp. 49-52 ◽  
Author(s):  
D. Galasko ◽  
M. R. Klauber ◽  
C. R. Hofstetter ◽  
D. P. Salmon ◽  
B. Lasker ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Hidetoshi Watari ◽  
Yutaka Shimada ◽  
Mie Matsui ◽  
Chihiro Tohda

Background and Aims. We previously reported that the administration of traditional Japanese medicines, kihito (Gui-Pi-Tang in Chinese) and kamikihito (Jia-Wei-Gui-Pi-Tang in Chinese), to Alzheimer’s disease (AD) model mice improved memory impairment. There are a few reports that show kihito and kamikihito have a beneficial effect on the cognitive function of AD patients in clinical studies. However, these studies are not comparative and are retrospective studies; thus, more evidence is needed. Therefore, we conducted an open-label, crossover designed clinical trial to investigate the effect of kihito on cognitive function of AD patients. Methods. The inclusion criteria for eligible patients were as follows: (1) imaging diagnosis (magnetic resonance imaging and single-photon emission computed tomography) of AD, (2) a treatment regimen including acetylcholinesterase inhibitors (ChEIs), and (3) a Mini-Mental State Examination (MMSE) score ≥15. The exclusion criteria were as follows: (1) change in ChEI dosage, (2) memantine usage, and (3) MMSE score < 15. To prevent bias in age and baseline cognitive function, patients were divided into two groups: the first group received 2.5 g of kihito extract 3 times/day during the first half of the study (weeks 0-16) and the second group received the same dose of kihito during the second half of the study (weeks 17-32). ChEI dosage did not change during the study period. Patients underwent a cognitive function test during weeks 0, 16, and 32. Cognitive function was evaluated by Japanese versions of the Mini-Mental State Examination (MMSE-J) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS-J) test. Results. Ten patients completed the clinical trial (4 males, 6 females, average age 71.7 years). MMSE-J scores significantly increased during the kihito intake period. RBANS-J test scores had a slight improvement during the kihito intake period compared with the ChEI alone treatment period, but no significant changes were observed. Conclusion. Kihito improves cognitive function in AD patients.


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