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.

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.

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 Evaluation of the neuroprotective effect of taurine in Alzheimer’s disease using functional molecular imaging

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Se Jong Oh ◽  
Hae-June Lee ◽  
Ye Ji Jeong ◽  
Kyung Rok Nam ◽  
Kyung Jun Kang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Imaging ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Brain Uptake ◽  
Positron Emission ◽  
Taurine Treatment

Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, but therapeutic treatment options are limited. Taurine has been reported to have neuroprotective properties against dementia, including AD. The present study aimed to investigate the treatment effect of taurine in AD mice by functional molecular imaging. To elucidate glutamate alterations by taurine, taurine was administered to 5xFAD transgenic mice from 2 months of age, known to apear amyloid deposition. Then, we performed glutamate positron emission tomography (PET) imaging studies for three groups (wild-type, AD, and taurine-treated AD, n = 5 in each group). As a result, brain uptake in the taurine-treated AD group was 31–40% higher than that in the AD group (cortex: 40%, p < 0.05; striatum: 32%, p < 0.01; hippocampus: 36%, p < 0.01; thalamus: 31%, p > 0.05) and 3–14% lower than that in the WT group (cortex: 10%, p > 0.05; striatum: 15%, p > 0.05; hippocampus: 14%, p > 0.05; thalamus: 3%, p > 0.05). However, we did not observe differences in Aβ pathology between the taurine-treated AD and AD groups in immunohistochemistry experiments. Our results reveal that although taurine treatment did not completely recover the glutamate system, it significantly increased metabolic glutamate receptor type 5 brain uptake. Therefore, taurine has therapeutic potential against AD.

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.

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.

scholarly journals An MRI-based strategy for differentiation of frontotemporal dementia and Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Qun Yu ◽  
◽  
Yingren Mai ◽  
Yuting Ruan ◽  
Yishan Luo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Frontotemporal Dementia ◽  
Brain Atrophy ◽  
Clinical Symptoms ◽  
Threshold Value ◽  
Imaging Biomarker ◽  
Independent Data ◽  
Significant Difference

Abstract Background The differential diagnosis of frontotemporal dementia (FTD) and Alzheimer’s disease (AD) is difficult due to the overlaps of clinical symptoms. Structural magnetic resonance imaging (sMRI) presents distinct brain atrophy and potentially helps in their differentiation. In this study, we aim at deriving a novel integrated index by leveraging the volumetric measures in brain regions with significant difference between AD and FTD and developing an MRI-based strategy for the differentiation of FTD and AD. Methods In this study, the data were acquired from three different databases, including 47 subjects with FTD, 47 subjects with AD, and 47 normal controls in the NACC database; 50 subjects with AD in the ADNI database; and 50 subjects with FTD in the FTLDNI database. The MR images of all subjects were automatically segmented, and the brain atrophy, including the AD resemblance atrophy index (AD-RAI), was quantified using AccuBrain®. A novel MRI index, named the frontotemporal dementia index (FTDI), was derived as the ratio between the weighted sum of the volumetric indexes in “FTD dominant” structures over that obtained from “AD dominant” structures. The weights and the identification of “FTD/AD dominant” structures were acquired from the statistical analysis of NACC data. The differentiation performance of FTDI was validated using independent data from ADNI and FTLDNI databases. Results AD-RAI is a proven imaging biomarker to identify AD and FTD from NC with significantly higher values (p < 0.001 and AUC = 0.88) as we reported before, while no significant difference was found between AD and FTD (p = 0.647). FTDI showed excellent accuracy in identifying FTD from AD (AUC = 0.90; SEN = 89%, SPE = 75% with threshold value = 1.08). The validation using independent data from ADNI and FTLDNI datasets also confirmed the efficacy of FTDI (AUC = 0.93; SEN = 96%, SPE = 70% with threshold value = 1.08). Conclusions Brain atrophy in AD, FTD, and normal elderly shows distinct patterns. In addition to AD-RAI that is designed to detect abnormal brain atrophy in dementia, a novel index specific to FTD is proposed and validated. By combining AD-RAI and FTDI, an MRI-based decision strategy was further proposed as a promising solution for the differential diagnosis of AD and FTD in clinical practice.

scholarly journals Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

2021 ◽  
Vol 14 (2) ◽  
pp. 110
Author(s):  
Caitlin Jie ◽  
Valerie Treyer ◽  
Roger Schibli ◽  
Linjing Mu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Second Generation ◽  
Tau Proteins ◽  
Tau Pathology ◽  
Pet Tracer ◽  
Positron Emission ◽  
Tau Pet ◽  
Target Binding

Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.

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.

Utilizing Advanced Imaging and Surrogate Markers Across the Spectrum of Alzheimer's Disease

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S18) ◽  
pp. 13-16 ◽  
Author(s):  
Mark A. Mintun
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Amyloid Plaques ◽  
Pet Tracer ◽  
Positron Emission ◽  
Amyloid Deposits ◽  
Wide Range ◽  
Β Amyloid ◽  
The Brain

AbstractAlzheimer's disease is a degenerative neurological condition characterized by the presence of β-amyloid plaques and neurofibrillary tangles in the limbic and neocortical regions of the brain. Pittsburgh Compound-B (PIB), a benzothiazole analog, has recently been found to specifically label amyloid deposits in positron emission tomography (PET) studies of the brain, opening the door for a wide range of applications related to Alzheimer's disease. In this article, data demonstrating the specificity of PIB as a PET tracer for β-amyloid lesions are reviewed, and the potential clinical applications of PIB PET imaging is discussed. Because amyloid plaques are common even in elderly individuals who are not suffering from dementia, the primary diagnostic function of PIB PET imaging presumably would be to rule out, rather than definitively confirm, Alzheimer's diagnoses in elderly patients. Other possible uses include monitoring plaque loads in patients receiving anti-amyloid therapy for Alzheimer's disease, as well as assessing plaque formation in unaffected individuals as a means of evaluating future Alzheimer's disease.

scholarly journals Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load

2021 ◽  
Author(s):  
Valeria Calsolaro ◽  
Paul M. Matthews ◽  
Cornelius K. Donat ◽  
Nicholas R. Livingston ◽  
Grazia D. Femminella ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Late Onset ◽  
Visual Assessment ◽  
Glial Fibrillary Acid Protein ◽  
Pet Tracer ◽  
Positron Emission ◽  
Cortical Regions

Abstract11C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer’s disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), 18F-florbetaben and 11C-BU99008 PET. The 8 amyloid (Aβ)-positive CI subjects had higher 11C-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between 11C-BU99008 and 18F-florbetaben. Autoradiography using 3H-BU99008 with post-mortem Alzheimer’s brains confirmed through visual assessment that increased 3H-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that 11C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer’s disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high Aβ load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.

Sign in / Sign up

Export Citation Format

Share Document