Biomarkers in Alzheimer’s disease

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Manuel H. Janeiro ◽  
Carlos G. Ardanaz ◽  
Noemí Sola-Sevilla ◽  
Jinya Dong ◽  
María Cortés-Erice ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Biological Fluids ◽  
Pathological Process ◽  
Positron Emission ◽  
Cerebrospinal Fluid Biomarkers ◽  
Novel Biomarkers ◽  
Definition Of ◽  
T Tau

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease. AD is the main cause of dementia worldwide and aging is the main risk factor for developing the illness. AD classical diagnostic criteria rely on clinical data. However, the development of a biological definition of AD using biomarkers that reflect the underling neuropathology is needed.ContentThe aim of this review is to describe the main outcomes when measuring classical and novel biomarkers in biological fluids or neuroimaging.SummaryNowadays, there are three classical biomarkers for the diagnosis of AD: Aβ42, t-Tau and p-Tau. The diagnostic use of cerebrospinal fluid biomarkers is limited due to invasive collection by lumbar puncture with potential side effects. Plasma/serum measurements are the gold standard in clinics, because they are minimally invasive and, in consequence, easily collected and processed. The two main proteins implicated in the pathological process, Aβ and Tau, can be visualized using neuroimaging techniques, such as positron emission tomography.OutlookAs it is currently accepted that AD starts decades before clinical symptoms could be diagnosed, the opportunity to detect biological alterations prior to clinical symptoms would allow early diagnosis or even perhaps change treatment possibilities.

The complexity of Alzheimer's disease: an evolving puzzle

2021 ◽  
Author(s):  
Sandro Sorbi ◽  
Camilla Ferrari
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
New Technologies ◽  
Clinical Symptoms ◽  
Real Life ◽  
Pathological Process ◽  
Point Of View ◽  
Biological Entity ◽  
History Of ◽  
Static View

The history of Alzheimer's disease (AD) started in 1907, but we needed to wait until the end of the century to identify the component of pathological hallmarks, genetic subtypes and to formulate the first pathogenic hypothesis. Thanks to biomarkers and new technologies, the concept of AD then rapidly changed from a static view of an amnestic dementia of the presenium to a biological entity that could be clinically manifested as normal cognition or dementia of different types. What is clearly emerging from studies is that AD is heterogeneous in each aspect, such as amyloid composition, tau distribution, relation between amyloid and tau, clinical symptoms, genetic background, and thus it is probably impossible to explain AD with a single pathological process. The scientific approach to AD suffers from chronological mismatches between clinical, pathological and technological data, causing difficulty in conceiving diagnostic gold standards and in creating models for drug discovery and screening. A recent mathematical computer-based approach offers the opportunity to study AD in real life and to provide a new point of view and the final missing pieces of the AD puzzle.

scholarly journals Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz2387 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Emelie Andersson ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Philip Insel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Phosphorylated Tau ◽  
Positron Emission ◽  
Aβ Aggregation ◽  
Tau Pet ◽  
5Xfad Mice ◽  
Tau Aggregation ◽  
T Tau

The links between β-amyloid (Aβ) and tau in Alzheimer’s disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.

scholarly journals Dielectric Constant and Conductivity of Blood Plasma: Possible Novel Biomarkers for Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ernest Dallé ◽  
Musa V. Mabandla ◽  
William M. U. Daniels
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dielectric Constant ◽  
Blood Plasma ◽  
Clinical Symptoms ◽  
Dorsal Hippocampus ◽  
Dependent Manner ◽  
Model Of Alzheimer’S Disease ◽  
Novel Biomarkers ◽  
New Treatments

Alzheimer’s disease is a complex debilitating neurodegenerative disease for which there is no cure. The lack of reliable biomarkers for Alzheimer’s disease has made the evaluation of the efficacy of new treatments difficult and reliant on only clinical symptoms. In an aged population where cognitive function may be deteriorating for other reasons, the dependence on clinical symptoms is also unreliable. However, it is well established that infusion of β-amyloid into the dorsal hippocampus of rats leads to cognitive impairment in a rat model of Alzheimer’s disease. Moreover, the blood plasma of β-amyloid-lesioned rats exhibits a distinct variation of the dielectric constant and conductivity when compared to that of normal rats in a time-dependent manner. These two electric parameters of blood plasma may therefore act as potential biomarkers for dementia due to Alzheimer’s disease. This review is aimed at highlighting evidences that support blood plasma electrical properties, e.g., dielectric constant and conductivity as possible novel biomarkers for the early development and progression of dementia due to Alzheimer’s disease.

scholarly journals Combined Study of Cerebral Glucose Metabolism and [11C]Methionine Accumulation in Probable Alzheimer's Disease Using Positron Emission Tomography

1996 ◽  
Vol 16 (3) ◽  
pp. 399-408 ◽  
Author(s):  
E. Salmon ◽  
M. C. Gregoire ◽  
G. Delfiore ◽  
C. Lemaire ◽  
C. Degueldre ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Glucose Metabolism ◽  
Clinical Symptoms ◽  
Synaptic Activity ◽  
Emission Tomography ◽  
Tissue Loss ◽  
Positron Emission

There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measured with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity.

Molecular Imaging in Alzheimer’s Disease

2011 ◽  
Vol 6 (1) ◽  
pp. 16
Author(s):  
Karl Herholz ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Imaging ◽  
Clinical Symptoms ◽  
Accurate Method ◽  
Imaging Biomarker ◽  
Pet Tracer ◽  
Specificity And Sensitivity ◽  
Positron Emission ◽  
Dementia Research

The most sensitive and accurate method for molecular imaging in human Alzheimer’s disease (AD) is positron emission tomography (PET). The most widely available PET tracer, which is also used in clinical oncology, is 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG is an imaging biomarker for early and differential diagnosis of AD. Even higher molecular specificity and sensitivity for detection of AD before dementia onset is provided by high-affinity ligands for fibrillary amyloid. 11C-Pittsburgh Compound B is widely being used in research laboratories, while new 18F-labelled ligands are currently undergoing formal clinical trials as amyloid imaging agents and are expected to become commercially available for clinical use in the near future. A large variety of tracers is being developed and used in dementia research for activated microglia and multiple neurotransmitter systems to study disease pathophysiology, biological correlates of clinical symptoms and new possibilities for treatment. Current studies in humans are investigating cholinergic, serotonergic and dopaminergic neurotransmission.

A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer’s Disease

2021 ◽  
pp. 1-8
Author(s):  
M. Senda ◽  
K. Ishii ◽  
K. Ito ◽  
T. Ikeuchi ◽  
H. Matsuda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Multicenter Study ◽  
Fdg Pet ◽  
Structural Mri ◽  
Amyloid Pet ◽  
Positron Emission ◽  
Prodromal Alzheimer’S Disease ◽  
T Tau

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the “ATN” (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer’s disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aβ1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

scholarly journals Protein Biomarkers for the Diagnosis of Alzheimer’s Disease at Different Stages of Neurodegeneration

2020 ◽  
Vol 21 (18) ◽  
pp. 6749
Author(s):  
Mar Pérez ◽  
Félix Hernández ◽  
Jesús Avila
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Biological Fluids ◽  
Protein Biomarkers ◽  
Familial Alzheimer’S Disease ◽  
Combined Use ◽  
Familial Alzheimer's Disease ◽  
Cellular Markers

Mainly obtained from familial Alzheimer’s disease patients’ data, we know that some features of the neurodegenerative start several years before the appearance of clinical symptoms. In this brief review, we comment on some molecular and cellular markers appearing at different stages of the disease, before or once the clinical symptoms are evident. These markers are present in biological fluids or could be identified by image techniques. The combined use of molecular and cellular markers will be of interest to determine the development of the different phases of the disease.

scholarly journals Contribution of genetic and environmental factors to the onset of preclinical Alzheimer’s disease - a monozygotic twin study

2020 ◽  
Author(s):  
Elles Konijnenberg ◽  
Jori Tomassen ◽  
Anouk den Braber ◽  
Mara ten Kate ◽  
Maqsood M. Yaqub ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Factors ◽  
Random Effect ◽  
Monozygotic Twin ◽  
Amyloid Pet ◽  
Positron Emission ◽  
Aβ Aggregation ◽  
T Tau ◽  
Aβ Production

AbstractObjectiveTo study the genetic contribution to the start of Alzheimer’s disease as signified by abnormalities in amyloid and tau biomarkers in cognitively intact older identical twins.MethodsWe studied in 96 monozygotic twin-pairs relationships between Aβ aggregation as measured by the ratio Aβ1-42/1-40 in cerebrospinal fluid (CSF) and positron emission tomography (PET), and CSF markers for Aβ production (BACE1, Aβ1-40 and 1-38) and tau. Associations amongst markers were tested with Generalized Estimating Equations including a random effect for twin status, adjusted for age, gender, and APOE ε4 genotype. We used twin analyses to determine relative contributions of genetic and/or environmental factors to AD pathophysiological processes.ResultsTwenty-seven individuals (14%) had an abnormal amyloid-PET, and 14 twin-pairs (15%) showed discordant amyloid status. Within twin-pairs, Aβ production markers and total-tau (t-tau) levels strongly correlated (r range 0.76, 0.88; all p<0.0001), and Aβ aggregation markers and 181-phosphorylated-tau (p-tau) levels correlated moderately strong (r range 0.49, 0.52; all p<0.0001). Cross-twin cross-trait analysis showed that Aβ1-38 in one twin correlated with Aβ1-42/1-40 ratios, t-tau and p-tau levels in their co-twins (r range 0.18, 0.58; all p<.07). Within-pair differences in Aβ production markers related to differences in tau levels (r range 0.49, 0.61; all p<0.0001). Twin discordance analyses suggest that Aβ production and tau levels show coordinated increases in very early AD.InterpretationOur results suggest a substantial genetic/shared environmental background contributes to both Aβ and tau increases, suggesting that modulation of environmental risk factors may aid in delaying the onset of AD pathophysiological processes.

Biomarkers for Alzheimer’s disease

2020 ◽  
pp. 99-116
Author(s):  
Andrea Vergallo ◽  
Harald Hampel ◽  
René S. Bun ◽  
Simone Lista
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Dynamic Range ◽  
Emission Tomography ◽  
Csf Biomarkers ◽  
Serum Proteomics ◽  
Positron Emission ◽  
T Tau ◽  
Technological Platforms

Reflecting the neuropathological hallmarks of Alzheimer’s disease (AD), cerebrospinal fluid (CSF) concentrations of Aβ‎1-42, t-tau, and p-tau and positive amyloid positron emission tomography (PET) imaging are considered core biomarkers for AD. Unfortunately, their use for screening is limited by their invasive nature (CSF biomarkers) or high cost (PET imaging). Among the biologic specimens that may be scrutinized for identifying novel AD biomarkers, circulating blood is a convenient source for sampling. The dynamic range of high-throughput technological platforms, coupled with advances in bioinformatics, holds the promise that proteomics will be a significant contributor to the field of blood-based AD biomarkers. Here, the chapter summarizes the blood-based biomarker platforms applied to the investigation of AD and reviews recent achievements in plasma/serum proteomics related to AD. These findings set the stage for the implementation of systems biology in the context of the evolving precision medicine paradigm for AD.

Molecular Imaging in Alzheimer’s Disease

US Neurology ◽  
2010 ◽  
Vol 06 (02) ◽  
pp. 28
Author(s):  
Karl Herholz ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Imaging ◽  
Clinical Symptoms ◽  
Accurate Method ◽  
Imaging Biomarker ◽  
Pet Tracer ◽  
Specificity And Sensitivity ◽  
Positron Emission ◽  
Dementia Research

The most sensitive and accurate method for molecular imaging in human Alzheimer’s disease (AD) is positron emission tomography (PET). The most widely available PET tracer, which is also used in clinical oncology, is 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG is an imaging biomarker for early and differential diagnosis of AD. Even higher molecular specificity and sensitivity for detection of AD before dementia onset is provided by high-affinity ligands for fibrillary amyloid. 11C-Pittsburgh Compound B is widely being used in research laboratories, while new 18F-labeled ligands are currently undergoing formal clinical trials as amyloid imaging agents and are expected to become commercially available for clinical use in the near future. A large variety of tracers is being developed and used in dementia research for activated microglia and multiple neurotransmitter systems to study disease pathophysiology, biological correlates of clinical symptoms, and new possibilities for treatment. Current studies in humans are investigating cholinergic, serotonergic, and dopaminergic neurotransmission.

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