scholarly journals The Potential Use of Blood, Cerebrospinal Fluid, Saliva and Urine as Biological Samples for the Diagnosis of Alzheimer’s Disease

2020 ◽  
pp. 26-41
Author(s):  
Adnan Awn Algarni ◽  
Abdulhadi I. Bima ◽  
Ayman Z. Elsamanoudy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Biological Samples ◽  
High Sensitivity ◽  
High Specificity ◽  
Clinical Criteria ◽  
Diagnosis And Prognosis ◽  
Positron Emission ◽  
Potential Use

Background and Aim: Alzheimer’s disease (AD) is the most common cause of dementia. 80% of all dementia is due to AD. Diagnosis of AD is a difficult task, as the accurate diagnosis requires post-mortem examination of brain autopsy samples. Diagnosis of AD in living individuals can be aided by the establishment of the clinical criteria, positron emission tomography (PET) examination, and biomarkers. The study of biomarkers for diagnosis of AD could help clinicians to evaluate individuals at risk, and confirm the occurrence as well as the progression of AD in a non-invasive manner. High sensitivity and high specificity of the used markers are mandatory criteria for these biomarkers to trusted for AD diagnosis and prognosis. So, this review article aims to focus on the potential use of body fluids as a source of the biomarkers that are used for investigating patients with AD. Methodology: In the current study, we reviewed scientific articles that discuss AD pathogenesis and diagnosis of Google Scholar database, Pubmed, Pubmed Central, Cochrane Database of Systematic Reviews (CDSR), MEDLINE, and MedlinePlus with no time limitation. Moreover, we discussed the use of recently discovered biomarkers that are detected in blood, CSF, saliva, and urine. Conclusion: In the current review, it could be concluded that in addition to the blood and cerebrospinal fluid as common biological samples for the diagnosis of AD, saliva and urine are useful potential biological samples. Moreover, both are noninvasive samples that give them priority to be used.

The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

2021 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Diyang Lyu ◽  
Jianping Jia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Dementia Patients ◽  
Positron Emission ◽  
Potential Biomarker ◽  
Synaptic Degeneration ◽  
Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

scholarly journals Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Better Than

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

scholarly journals Quantitative Measurement of Cerebrospinal Fluid Amyloid-β Species by Mass Spectrometry

2020 ◽  
pp. 1-12
Author(s):  
Yusuke Seino ◽  
Takumi Nakamura ◽  
Tomoo Harada ◽  
Naoko Nakahata ◽  
Takeshi Kawarabayashi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Quantitative Measurement ◽  
Amyloid Β ◽  
High Sensitivity ◽  
Csf Biomarkers ◽  
Strongly Correlated ◽  
Csf Levels

Background: High sensitivity liquid chromatography mass spectrometry (LC-MS/MS) was recently introduced to measure amyloid-β (Aβ) species, allowing for a simultaneous assay that is superior to ELISA, which requires more assay steps with multiple antibodies. Objective: We validated the Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-43 assay by LC-MS/MS and compared it with ELISA using cerebrospinal fluid (CSF) samples to investigate its feasibility for clinical application. Methods: CSF samples from 120 subjects [8 Alzheimer’s disease (AD) with dementia (ADD), 2 mild cognitive dementia due to Alzheimer’s disease (ADMCI), 14 cognitively unimpaired (CU), and 96 neurological disease subjects] were analyzed. Aβ species were separated using the Shimadzu Nexera X2 system and quantitated using a Qtrap 5500 LC-MS/MS system. Aβ1-40 and Aβ1-42 levels were validated using ELISA. Results: CSF levels in CU were 666±249 pmol/L in Aβ1-38, 2199±725 pmol/L in Aβ1-40, 153.7±79.7 pmol/L in Aβ1-42, and 9.78±4.58 pmol/L in Aβ1-43. The ratio of the amounts of Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-43 was approximately 68:225:16:1. Linear regression analyses showed correlations among the respective Aβ species. Both Aβ1-40 and Aβ1-42 values were strongly correlated with ELISA measurements. No significant differences were observed in Aβ1-38 or Aβ1-40 levels between AD and CU. Aβ1-42 and Aβ1-43 levels were significantly lower, whereas the Aβ1-38/1-42, Aβ1-38/1-43, and Aβ1-40/Aβ1-43 ratios were significantly higher in AD than in CU. The basic assay profiles of the respective Aβ species were adequate for clinical usage. Conclusion: A quantitative LC-MS/MS assay of CSF Aβ species is as reliable as specific ELISA for clinical evaluation of CSF biomarkers for AD.

scholarly journals Biomarkers for Alzheimer’s Disease Early Diagnosis

2020 ◽  
Vol 10 (3) ◽  
pp. 114 ◽  
Author(s):  
Eva Ausó ◽  
Violeta Gómez-Vicente ◽  
Gema Esquiva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Loss ◽  
Diagnostic Tools ◽  
Csf Biomarkers ◽  
Diagnosis And Prognosis ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

AD Resemblance Atrophy Index as a Diagnostic Biomarker for Alzheimer’s Disease: A Retrospective Clinical and Biological Validation

2021 ◽  
Vol 79 (3) ◽  
pp. 1023-1032
Author(s):  
Yingren Mai ◽  
Qun Yu ◽  
Feiqi Zhu ◽  
Yishan Luo ◽  
Wang Liao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Structure ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Clinical Scenario ◽  
Clinical Criteria ◽  
Positron Emission ◽  
And Gender ◽  
Sensitivity Specificity

Background: Magnetic resonance imaging (MRI) provides objective information about brain structural atrophy in patients with Alzheimer’s disease (AD). This multi-structural atrophic information, when integrated as a single differential index, has the potential to further elevate the accuracy of AD identification from normal control (NC) compared to the conventional structure volumetric index. Objective: We herein investigated the performance of such an MRI-derived AD index, AD-Resemblance Atrophy Index (AD-RAI), as a neuroimaging biomarker in clinical scenario. Method: Fifty AD patients (19 with the Amyloid, Tau, Neurodegeneration (ATN) results assessed in cerebrospinal fluid) and 50 age- and gender-matched NC (19 with ATN results assessed using positron emission tomography) were recruited in this study. MRI-based imaging biomarkers, i.e., AD-RAI, were quantified using AccuBrain®. The accuracy, sensitivity, specificity, and area under the ROC curve (AUC) of these MRI-based imaging biomarkers were evaluated with the diagnosis result according to clinical criteria for all subjects and ATN biological markers for the subgroup. Results: In the whole groups of AD and NC subjects, the accuracy of AD-RAI was 91%, sensitivity and specificity were 88% and 96%, respectively, and the AUC was 92%. In the subgroup of 19 AD and 19 NC with ATN results, AD-RAI results matched completely with ATN classification. AD-RAI outperforms the volume of any single brain structure measured. Conclusion: The finding supports the hypothesis that MRI-derived composite AD-RAI is a more accurate imaging biomarker than individual brain structure volumetry in the identification of AD from NC in the clinical scenario.

scholarly journals ACCURACY OF NEUROPSYCHOLOGICAL TESTS IN PATIENTS WITH BIOLOGICAL DIAGNOSIS OF ALZHEIMER’S DISEASE

2021 ◽  
Author(s):  
Patrícia Peles ◽  
Larissa Salvador ◽  
Luciano Mariano ◽  
Viviane Carvalho ◽  
Clarisse Frieldlaender ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychological Tests ◽  
Rating Scale ◽  
Digit Span ◽  
Verbal Learning ◽  
High Sensitivity ◽  
High Specificity ◽  
Adult Intelligence Scale ◽  
Wechsler Adult Intelligence Scale

Background: Neuropsychological tests are important tools for the diagnosis of mild cognitive impairment or dementia due to Alzheimer’s disease (AD). Objective: To investigate the accuracy of common neuropsychological tests used in the clinical setting for AD diagnosis. Methods: Forty two patients with diagnosis of AD continuum [A+T+/-(N)+/-] and 32 non-AD [A-T+/-(N)+/-]. All participants were submitted to a thorough neuropsychological assessment with the following instruments: Mattis Dementia Rating Scale (DRS), Rey’s Auditory Verbal Learning Test (RAVLT), Boston naming-Consortium to Establish a Registry for Alzheimer’s Disease, a reduced version of the CERAD, Digit Span Forward (DSF), Digit Span Backward (DSB) and Cubes from The Wechsler Adult Intelligence Scale (WAIS), verbal fluency – animals (VF-A), and FAS. Results: Memory (MEM) and Initiation/Perseveration (I/P) subscales of the DRS, FAS, Digit Span Backward (DSB) and Boston naming displayed good discrimination between AD and non-AD patients. The MEM subscale of the DRS, RAVLT A6 and FAS presented high sensitivity (90% or more) for AD diagnosis, while DSF displayed high specificity. Non-AD patients had greater difficulty in FAS, DSB and in Boston naming. Conclusion: Performance of patients with biological diagnosis of AD on MEM and I/P of DRS, and RAVLT A7 was significantly different from that of non-AD subjects.

scholarly journals Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use

2020 ◽  
Vol 10 (3) ◽  
pp. 116 ◽  
Author(s):  
Cristina d’Abramo ◽  
Luciano D’Adamio ◽  
Luca Giliberto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
High Sensitivity ◽  
Brain Parenchyma ◽  
Metabolic Derangement ◽  
In Vivo Diagnosis ◽  
Definition Of ◽  
Sensitivity Specificity

Alzheimer’s disease (AD) is the most common type of dementia, affecting more than 5 million Americans, with steadily increasing mortality and incredible socio-economic burden. Not only have therapeutic efforts so far failed to reach significant efficacy, but the real pathogenesis of the disease is still obscure. The current theories are based on pathological findings of amyloid plaques and tau neurofibrillary tangles that accumulate in the brain parenchyma of affected patients. These findings have defined, together with the extensive neurodegeneration, the diagnostic criteria of the disease. The ability to detect changes in the levels of amyloid and tau in cerebrospinal fluid (CSF) first, and more recently in blood, has allowed us to use these biomarkers for the specific in-vivo diagnosis of AD in humans. Furthermore, other pathological elements of AD, such as the loss of neurons, inflammation and metabolic derangement, have translated to the definition of other CSF and blood biomarkers, which are not specific of the disease but, when combined with amyloid and tau, correlate with the progression from mild cognitive impairment to AD dementia, or identify patients who will develop AD pathology. In this review, we discuss the role of current and hypothetical biomarkers of Alzheimer’s disease, their specificity, and the caveats of current high-sensitivity platforms for their peripheral detection.

Amyloid-β and Hyperphosphorylated Tau in the Prediction of Alzheimer’s Disease

2011 ◽  
Vol 6 (2) ◽  
pp. 84
Author(s):  
Jaana Rummukainen ◽  
Anne M Koivisto ◽  
Irina Alafuzoff ◽  
Ville Leinonen ◽  
◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Brain Biopsy ◽  
High Sensitivity ◽  
High Specificity ◽  
Normal Pressure ◽  
Early Event ◽  
Hyperphosphorylated Tau ◽  
Low Sensitivity

Brain amyloid-β (Aβ) deposition is widely believed to be an early event in Alzheimer’s disease (AD). Aβ plaques, along with intracellular neurofibrillary tangles, which largely comprise hyperphosphorylated tau (HPτ), are considered to be neuropathological hallmarks of AD. Brain biopsies from living subjects could be used to evaluate these findings. It is possible to obtain biopsies from patients with presumed normal pressure hydrocephalus during diagnostic or shunt procedures. The presence of both Aβ and HPτ in frontal cortex biopsy samples seems to be a strong indicator of AD with high specificity (98 %) but rather low sensitivity (36 %). Aβ alone is associated with AD and exhibits high sensitivity (87 %) but lower specificity (69 %), indicating that many patients with Aβ only may also develop clinical dementia other than AD. Although a definite diagnosis of AD can only be confirmed at autopsy, brain biopsies may be useful for identification of novel markers of AD in a research context. In addition, when available, brain biopsy can be a useful diagnostic aid and validate non-invasive techniques in the diagnosis of dementia.

scholarly journals Cerebrospinal Fluid BACE1 Activity and Brain Amyloid Load in Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Timo Grimmer ◽  
Panagiotis Alexopoulos ◽  
Amalia Tsolakidou ◽  
Liang-Hao Guo ◽  
Gjermund Henriksen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Linear Regression Analysis ◽  
Tracer Uptake ◽  
Amyloid Pathology ◽  
Positron Emission ◽  
Amyloid Load ◽  
Bace1 Activity

The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([11C]PIB PET). [11C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [11C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.

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