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Alzheimer's disease (AD) is the most common cause of dementia in elderly subjects. AD is characterized by brain lesions like extracellular deposits of ß-amyloïd proteins in senile plaques and intracellular neurofibrillary tangles of hyper-phosphorylated tau protein, both of which are associated with the loss of neurons. The development of disease biomarkers for AD (Tau, PhTau and βamyloid dosing in the cerebrospinal fluid, brain MRI, amyloid PET imaging and fluorodeoxyglucose PET imaging) to identify the pathophysiological processes underlying cognitive impairment biomarkers, have been incorporated into revised diagnosis guidelines.
Post-mortem human AD and AD animal model studies have reported inflammatory processes also implicated in the neuropathology of AD, and upregulated levels of pro-inflammatory cytokines.
In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands (tracers) for use with positron emission tomography (PET). The translocator protein (TSPO) formerly known as the peripheral benzodiazepine receptor (PBR), a receptor located in the outer membrane of mitochondria, is upregulated during neuroinflammation. So targeting TSPO with radiolabeled ligands for PET is considered as an attractive biomarker for neuroinflammation.
The main aim of this pilot study is to quantify neuroinflammation, in terms of fixation and distribution of [18F] DPA-714(Binding Potential BP), and to study its relationship with amyloid load, measured with in [18F]AV-45 (Standard Uptake Values ratio) in cognitive decline.
Molecular imaging of microglial activation could help us document the central inflammatory status of study subjects and assist us in designing future research studies particularly with respect to which subjects to enrol into clinical trials and to evaluate the benefit of specific therapies in selected groups, for example, by monitoring the effects of Aß immunization.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Memory complaint /MCI/ mild to moderate MA | Experimental | Memory complaint (without cognitive decline): 12 patients/ Mild Cognitive Impairment: 12 patients/ Mild to moderate Alzheimer Disease: 12 patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [18F]DPA-714 PET/ [18F]AV-45 PET/neuropsychological assessment | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Fixation and distribution of [18F]DPA-714 (Binding Potential BP) | 2 years | |
| [18F]AV-45 Standard Uptake Values ratio | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Relationship between [18F]DPA-714 uptake and cognitive, affective symptoms at baseline. | 2 years |
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Inclusion Criteria:
Criteria common to all participants:
Criteria for patients with mild to moderate Alzheimer disease defined according to the NINCDS-ADRDA {McKhann, 2011 # 408}:
Criteria for amnestic MCI patients:
Criteria for patients with isolated memory Complaint (Without Cognitive Decline):
No inclusion criteria :
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| Name | Affiliation | Role |
|---|---|---|
| Emilie BEAUFILS, PhD | University Hospital of Tours (CMRR) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Tours | Tours | 37000 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22172392 | Result | Arlicot N, Vercouillie J, Ribeiro MJ, Tauber C, Venel Y, Baulieu JL, Maia S, Corcia P, Stabin MG, Reynolds A, Kassiou M, Guilloteau D. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol. 2012 May;39(4):570-8. doi: 10.1016/j.nucmedbio.2011.10.012. Epub 2011 Dec 14. | |
| 22252372 |
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| Camus V, Payoux P, Barre L, Desgranges B, Voisin T, Tauber C, La Joie R, Tafani M, Hommet C, Chetelat G, Mondon K, de La Sayette V, Cottier JP, Beaufils E, Ribeiro MJ, Gissot V, Vierron E, Vercouillie J, Vellas B, Eustache F, Guilloteau D. Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment. Eur J Nucl Med Mol Imaging. 2012 Apr;39(4):621-31. doi: 10.1007/s00259-011-2021-8. Epub 2012 Jan 18. |
| 23152610 | Result | La Joie R, Perrotin A, Barre L, Hommet C, Mezenge F, Ibazizene M, Camus V, Abbas A, Landeau B, Guilloteau D, de La Sayette V, Eustache F, Desgranges B, Chetelat G. Region-specific hierarchy between atrophy, hypometabolism, and beta-amyloid (Abeta) load in Alzheimer's disease dementia. J Neurosci. 2012 Nov 14;32(46):16265-73. doi: 10.1523/JNEUROSCI.2170-12.2012. |
| 22986776 | Result | Beaufils E, Dufour-Rainfray D, Hommet C, Brault F, Cottier JP, Ribeiro MJ, Mondon K, Guilloteau D. Confirmation of the amyloidogenic process in posterior cortical atrophy: value of the Abeta42/Abeta40 ratio. J Alzheimers Dis. 2013;33(3):775-80. doi: 10.3233/JAD-2012-121267. |
| 23300829 | Result | Corcia P, Tauber C, Vercoullie J, Arlicot N, Prunier C, Praline J, Nicolas G, Venel Y, Hommet C, Baulieu JL, Cottier JP, Roussel C, Kassiou M, Guilloteau D, Ribeiro MJ. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One. 2012;7(12):e52941. doi: 10.1371/journal.pone.0052941. Epub 2012 Dec 31. |
| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
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