Plasma Levels of Amyloid-β Peptides and Tau Protein in Mexican Patients with Alzheimer’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Tzayaka Castillo-Mendieta ◽  
Yoaly Arana-Lechuga ◽  
Victoria Campos-Peña ◽  
Ana Luisa Sosa ◽  
Sandra Orozco-Suarez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Amyloid Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Plasma Biomarkers ◽  
Control Subjects ◽  
And Control ◽  
T Tau

Background: Alzheimer’s disease (AD) causes memory deficit and alterations in other cognitive functions, mainly in adults over 60 years of age. As the diagnosis confirmation is performed by a postmortem neuropathological examination of the brain, this disease can be confused with other types of dementia at early stages. About 860,000 Mexicans are affected by dementia, most of them with insufficient access to adequate comprehensive health care services. Plasma biomarkers could be a rapid option for early diagnosis of the disease. Objective: This study aimed to analyze some plasma biomarkers (amyloid-β, tau, and lipids) in Mexican AD patients and control subjects with no associated neurodegenerative diseases. Methods: Plasma amyloid-β peptides (Aβ 40 and Aβ 42), total and phosphorylated tau protein (T-tau and P-tau), and cholesterol and triglyceride levels were quantified enzyme-linked immunosorbent assay in AD patients and control subjects. Results: In Mexican AD patients, we found significantly lower levels of Aβ 42 (p <  0.05) compared to the control group. In contrast, significantly higher levels of P-tau (p <  0.05) and triglycerides (p <  0.05) were observed in AD patients compared to controls. Furthermore, a significant correlation was found between the severity of dementia and plasma P-tau levels, Aβ 42/Aβ 40 and P-tau/T-tau ratios, and triglycerides concentrations. This correlation increased gradually with cognitive decline. Conclusion: The detection of these plasma biomarkers is an initial step in searching for a timely, less invasive, and cost-efficient diagnosis in Mexicans.

scholarly journals Performance of Plasma Amyloid β, Total Tau and Neurofilament Light Chain Levels for Alzheimer’s Disease Identification

2020 ◽  
Author(s):  
Bin Jiao ◽  
Hui Liu ◽  
Lina Guo ◽  
Xinxin Liao ◽  
Yafang Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Light Chain ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Total Tau ◽  
T Tau

Abstract BackgroundRobust studies have focused on blood-based biomarkers for diagnosis of Alzheimer’s disease (AD), while the results were still controversary and failed verified in different cohorts. The aim of this study was to detect the levels of plasma amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL) in patients with AD and cognitive normal (CN) subjects, and clarify their associations with Aβ, t-tau, and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as well as brain amyloid PET, and calculate the diagnostic efficiency of these characteristics regarding AD.Methods Plasma Aβ42, Aβ40, t-tau and NfL levels were detected by single-molecule array (Simoa) in 379 AD patients and 153 CN subjects. Additionally, lumbar puncture was conducted in 125 AD patients to detect Aβ42, Aβ40, t-tau, and p-tau levels. Brain amyloid PET was performed in 52 AD patients to identify brain amyloid deposition levels. Correlation analysis were performed between plasma biomarkers and typical biomarkers of AD, including CSF core biomarkers and amyloid PET burden. Finally, the diagnostic value of plasma biomarkers was further assessed by receiver operating characteristic (ROC) curve.ResultsCompared with the CN group, plasma Aβ42 and Aβ42/Aβ40 levels were significantly lower in AD patients, while Aβ40, t-tau and NfL levels were higher in AD patients. Among the AD patients, plasma Aβ42 was positively correlated with CSF Aβ42 (r = 0.195, p = 0.03) and Aβ42/Aβ40 (r = 0.208, p = 0.04). Moreover, plasma NfL was positively correlated with age, disease course and severity. The diagnostic model with combined plasma Aβ42, t-tau, and NfL levels controlled for age and APOE genotype showed the best performance to identify AD (area under the curve (AUC) = 0.88, sensitivity = 82.84%, specificity = 81.69%, cutoff value = 0.64).ConclusionsTrends revealed by core biomarkers were generally consistent in AD patients’ plasma and CSF. Combining plasma biomarkers can provide comparatively high AD diagnostic performance.

scholarly journals Platelet Tau Protein as a Potential Peripheral Biomarker in Alzheimer’s Disease: An Explorative Study

2018 ◽  
Vol 15 (9) ◽  
pp. 800-808 ◽  
Author(s):  
Elizabeta B. Mukaetova-Ladinska ◽  
Zeinab Abdell-All ◽  
Joana Andrade ◽  
Joaquim Alves da Silva ◽  
Irina Boksha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Blood Platelets ◽  
Neuronal Cell ◽  
Clinical Settings ◽  
Neuronal Cell Lines ◽  
Specific Proteins ◽  
And Control ◽  
T Tau

Background: Cerebrospinal fluid (CSF) measures of tau and amyloid proteins have now been largely accepted to be a diagnostic tool to aid the clinical diagnosis of Alzheimer's disease (AD), but CSF is not routinely obtained in most clinical settings. There is a need, therefore, to uncover additional readily accessible peripheral biomarkers that will enable comprehensive detection of AD-specific proteins in blood and blood derivates. Objectives: Blood platelets contain proteins found in neuronal cell lines, including tau protein. Since tau protein is a characteristic of AD-neuropathology, platelet tau protein may be closely related to the central nervous process occurring in neurodegeneration. Method: Platelets from 25 AD and 26 control subjects were analysed for the microtubule-binding and C-terminal region, as well as two tau phosphorylation sites (Ser202/Thr205 and Thr181). Results: Tau protein measures did not discriminate between AD and control individuals. However, subjects with MMSE 24-27 had elevated C-terminal end tau protein (p=0.049) compared to those with MMSE >27, whereas older AD subjects (>80 years) showed higher t-tau protein in comparison to younger AD (<80 years; p=0.009) and control (<80 years; p=0.011) participants. Conclusions: These initial findings not only confirm that platelet tau protein can be measured, but also indicate that platelet tau measures merit further study as they may be useful in indicating early stages of cognitive impairment. Further studies on larger number of participants are needed to confirm our findings.

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 A Non-APOE Polygenic Risk Score for Alzheimer’s Disease Is Associated With Cerebrospinal Fluid Neurofilament Light in a Representative Sample of Cognitively Unimpaired 70-Year Olds

2021 ◽  
Author(s):  
Ingmar Skoog ◽  
Silke Kern ◽  
Jenna Najar ◽  
Rita Guerreiro ◽  
Jose Bras ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Polygenic Risk Score ◽  
Neurofilament Light ◽  
Polygenic Risk ◽  
Apoe Ε4 ◽  
T Tau

Abstract The effect of Alzheimer’s disease (AD) polygenic risk scores (PRS) on amyloid and tau pathophysiology and neurodegeneration in cognitively unimpaired older adults is not known in detail. This study aims to investigate non-APOE AD-PRS and APOE ε4 in relation to AD pathophysiology evaluated by cerebrospinal fluid (CSF) biomarkers in a population-based sample of 70-year olds. A total of 303 dementia-free individuals from the Gothenburg H70 Birth Cohort Studies were included. Genotyping was performed using the NeuroChip, and AD-PRS were calculated. CSF levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), neurogranin (Ng), and neurofilament light (NfL) were measured with enzyme-linked immunosorbent assay. Associations were found between non-APOE PRS and both NfL (p = .001) and Aβ42 (p = .02), and between APOE ε4 and Aβ42 (p = 1e−10), t-tau (p = 5e−4), and p-tau (p = .002). Similar results were observed when only including individuals with CDR = 0, except for no evidence of an association between non-APOE PRS and Aβ42. There was an interaction between non-APOE PRS and Aβ42 pathology status in relation to NfL (p = .005); association was only present in individuals without Aβ42 pathology (p = 3e-4). In relation to Aβ42, there was a borderline interaction (p = .06) between non-APOE PRS and APOE ε4; association was present in ε4 carriers only (p = .03). Similar results were observed in individuals with CDR = 0 (n = 246). In conclusion, among cognitively healthy 70-year olds from the general population, genetic risk of AD beyond the APOE locus was associated with NfL in individuals without Aβ42 pathology, and with Aβ42 in APOE ε4 carriers, suggesting these associations are driven by different mechanisms.

scholarly journals Neuroprotective Effects of Cistanches Herba Therapy on Patients with Moderate Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Nan Li ◽  
Jianping Wang ◽  
Jun Ma ◽  
Zhiqiang Gu ◽  
Chao Jiang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Independent Living ◽  
Control Group ◽  
Mrna Levels ◽  
Volume Changes ◽  
Neuroprotective Effects ◽  
Mri Scans ◽  
And Control ◽  
T Tau

Cistanches Herba (CH) is thought to be a “Yang-invigorating” material in traditional Chinese medicine. We evaluated neuroprotective effects of Cistanches Herba on Alzheimer’s disease (AD) patients. Moderate AD participants were divided into 3 groups: Cistanches Herba capsule (CH,n=10), Donepezil tablet (DON,n=8), and control group without treatmentn=6. We assessed efficacy by MMSE and ADAS-cog, and investigated the volume changes of hippocampus by 1.5 T MRI scans. Protein, mRNA levels, and secretions of total-tau (T-tau), tumor necrosis factor-α(TNF-α), and interleukin- (IL) 1β(IL-1β) in cerebrospinal fluid (CSF) were detected by Western blot, RT-PCR, and ELISA. The scores showed statistical difference after 48 weeks of treatment compared to control group. Meanwhile, volume changes of hippocampus were slight in drug treatment groups but distinct in control group; the levels of T-tau, TNF-α, and IL-1βwere decreased compared to those in control group. Cistanches Herba could improve cognitive and independent living ability of moderate AD patients, slow down volume changes of hippocampus, and reduce the levels of T-tau, TNF-α, and IL-1β. It suggested that Cistanches Herba had potential neuroprotective effects for moderate AD.

The Correlation of Tau Levels with Blood Monocyte Count in Patients with Alzheimer’s Disease

2021 ◽  
pp. 1-8
Author(s):  
Hao-Lun Sun ◽  
Fa-Ying Zhou ◽  
Dong-Wan Chen ◽  
Cheng-Rong Tan ◽  
Gui-Hua Zeng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Amyloid Β ◽  
Blood Monocyte ◽  
Monocyte Count ◽  
Cognitively Normal ◽  
T Tau ◽  
Normal Controls ◽  
Age And Sex

Background: Recent studies have shown that monocytes can phagocytize the tau protein, which may ameliorate tau-type pathology in Alzheimer’s disease (AD). However, there are few clinical studies on the relationship between monocytes and tau-type pathology in AD patients. Objective: We aimed to explore changes in peripheral monocytes and their association with tau protein in AD patients. Methods: A total of 127 clinically diagnosed AD patients and 100 age- and sex-matched cognitively normal controls were recruited for analysis of the correlation of plasma tau levels with the blood monocyte count. Cerebrospinal fluid (CSF) samples from 46 AD patients and 88 controls were further collected to analyze the correlation of CSF tau and amyloid-β (Aβ) levels with the blood monocyte count. 105 clinically diagnosed mild cognitive impairment (MCI) patients and 149 age- and sex-matched cognitively normal controls were recruited from another cohort for verification. Results: Compared to normal controls, AD patients showed a significant reduction in the blood monocyte count. In addition, the monocyte count of AD patients was negatively correlated with CSF t-tau and p-tau levels but not with plasma tau levels. In normal people, monocyte count lack correlation with tau levels both in plasma and CSF. Monocyte count were not correlated with CSF Aβ levels in either group but were negatively correlated with CSF tau/Aβ 42 levels in the AD group. We had further verified the correlations of monocyte count with CSF tau levels in another cohort. Conclusion: This study suggests that monocytes may play an important role in the clearance of tau protein in the brain.

scholarly journals Cerebrospinal fluid amyloid beta and tau protein: Biomarkers for Alzheimer's disease

2008 ◽  
Vol 65 (12) ◽  
pp. 901-905
Author(s):  
Gorana Mandic ◽  
Ivanka Markovic ◽  
Marija Ostojic ◽  
Tanja Stojkovic ◽  
Sonja Misirlic-Dencic ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Tau Protein ◽  
Symptomatic Treatment ◽  
Amyloid Peptide ◽  
Control Group ◽  
Csf Biomarkers ◽  
Diagnostic Potential ◽  
T Tau

Background/Aim. Introduction of acetylcholine esterase inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has additionally highlighted the importance of diagnostic markers in cerebrospinal fluid (CSF) for early AD diagnosis: low level of 42 amino acid form of amyloid-? peptide (A?42), and levels of tau protein (T-tau) and phosphorylated tau protein (P-tau). The aim of this study was to diagnostic potential of CSF biomarkers T-tau, P-tau and A?42 as biochemical markers for AD. Methods. Lumbar puncture was performed in 63 patients with AD and 26 control subjects who passed orthopedic surgery. The Innotest, ELISA sandwich test (Innogenetics - Belgium) was used for measuring the levels of T-tau, P-tau and A?42. Results. The patients and the control group did not differ in age, education and sex. Mean levels of CSF T-tau and P-tau were significantly higher in the patients with AD (p < 0.001) compared to the control group, in contrast to significantely lower CSF A?42 in AD group (p < 0.001). A significant progressive decrease of A?42, as well as significant progressive increase of T-tau and P-tau was found among AD subgroups (according to MMSE staging) and controls. Conclusion. The obtained results suggest that these biomarkers may be supportive in the diagnosis of AD, especially in the early course of the disease and could be used in the routine clinical practice considering the approaching target therapeutics.

scholarly journals Performance of Plasma Amyloid β, Total Tau, and Neurofilament Light Chain in the Identification of Probable Alzheimer's Disease in South China

2021 ◽  
Vol 13 ◽  
Author(s):  
Bin Jiao ◽  
Hui Liu ◽  
Lina Guo ◽  
Xinxin Liao ◽  
Yafang Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Correlation Analysis ◽  
Light Chain ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Total Tau ◽  
T Tau

Background: Alzheimer's disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population.Methods: A total of 277 patients with a clinical diagnosis of probable AD and 153 healthy controls with normal cognitive function (CN) were enrolled in this study. The levels of plasma Aβ42, Aβ40, t-tau, and NfL were detected using ultra-sensitive immune-based assays (SIMOA). Lumbar puncture was conducted in 89 patients with AD to detect Aβ42, Aβ40, t-tau, and phosphorylated (p)-tau levels in the cerebrospinal fluid (CSF) and to evaluate the consistency between plasma and CSF biomarkers through correlation analysis. Finally, the diagnostic value of plasma biomarkers was further assessed by constructing a receiver operating characteristic (ROC) curve.Results: After adjusting for age, sex, and the apolipoprotein E (APOE) alleles, compared to the CN group, the plasma t-tau, and NfL were significantly increased in the AD group (p &lt; 0.01, Bonferroni correction). Correlation analysis showed that only the plasma t-tau level was positively correlated with the CSF t-tau levels (r = 0.319, p = 0.003). The diagnostic model combining plasma t-tau and NfL levels, and age, sex, and APOE alleles, showed the best performance for the identification of probable AD [area under the curve (AUC) = 0.89, sensitivity = 82.31%, specificity = 83.66%].Conclusion: Blood biomarkers can effectively distinguish patients with probable AD from controls and may be a non-invasive and efficient method for AD pre-screening.

Follow-up study on plasma and cerebrospinal fluid levels of B amyloids and tau proteins in patients with alzheimer's disease

2011 ◽  
Vol 26 (S2) ◽  
pp. 506-506
Author(s):  
Y. Fu ◽  
S. Xiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Levels ◽  
Severity Of Dementia ◽  
T Tau

AimsCompare baseline and 6-month follow-up plasma and cerebrospinal fluid (CSF) levels of amyloid β peptides 1–40 (Aβ1–40) and 1–42 (Aβ1–42), total tau protein (T-tau) and phosphorylated tau at threonine 231 (P-tau231) in patients with Alzheimer's disease (AD) and vascular dementia (VD).Methods21 patients with AD and 7 patients with VD based on the criteria of Diagnostic Statistical Manual 4th edition were assessed at baseline and 7 with AD and 6 with VD were re-assessed 6 months later. Assessments included the Mini-Mental State Exam (MMSE), the Global Deteriorate Scale (GDS), plasma and CSF levels of Aβ1–40 and Aβ1–42, and CSF levels of T-tau and P-tau231 (using a sandwich enzyme-linked immunosorbent assay).ResultsAt baseline there were significant differences between AD and VD patients in the mean CSF levels of T-tau (t=2.580, P=0.016), P-tau231 (t=4.014, P=0.000) and Aβ1–40 (t=2.766, P=0.010). At baseline in AD patients, duration of illness was negatively correlated with CSF P-tau231 levels (r=-0.485, P=0.026), MMSE scores (r=-0.565, P=0.008) and GDS scores (r=-0.482, P=0.027); and CSF Aβ1–42 levels were positively correlated to MMSE scores (r=0.565, P=0.008) and negatively correlated with GDS scores (r=-0.634, P=0.002). In the AD patients plasma Aβ1–40 levels increased significantly over the 6-month follow-up period (t=-2.735, P=0.041).ConclusionsPlasma Aβ1–40 levels increased significantly in AD patients after 6-months of follow-up, that means levels of plasma Aβ1–40 could imply the development of Alzheimer disease. Moreover, CSF P-tau231 and CSF Aβ1–42 levels are associated with the severity of dementia and cognitive impairment.

A Numerical Study of Sensitivity Coefficients for a Model of Amyloid Precursor Protein and Tubulin-Associated Unit Protein Transport and Agglomeration in Neurons at the Onset of Alzheimer's Disease

2019 ◽  
Vol 141 (3) ◽  
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Tau Protein ◽  
Protein Transport ◽  
Numerical Study ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Model Parameters ◽  
In The Beginning

Modeling of intracellular processes occurring during the development of Alzheimer's disease (AD) can be instrumental in understanding the disease and can potentially contribute to finding treatments for the disease. The model of intracellular processes in AD, which we previously developed, contains a large number of parameters. To distinguish between more important and less important parameters, we performed a local sensitivity analysis of this model around the values of parameters that give the best fit with published experimental results. We show that the influence of model parameters on the total concentrations of amyloid precursor protein (APP) and tubulin-associated unit (tau) protein in the axon is reciprocal to the influence of the same parameters on the average velocities of the same proteins during their transport in the axon. The results of our analysis also suggest that in the beginning of AD the aggregation of amyloid-β and misfolded tau protein have little effect on transport of APP and tau in the axon, which suggests that early damage in AD may be reversible.

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