scholarly journals In Vivo TSPO Signal and Neuroinflammation in Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1941 ◽  
Author(s):  
Benjamin B. Tournier ◽  
Stergios Tsartsalis ◽  
Kelly Ceyzériat ◽  
Valentina Garibotto ◽  
Philippe Millet
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Time Course ◽  
Single Photon ◽  
Photon Emission ◽  
Cell Types ◽  
Translocator Protein ◽  
Emission Computed Tomography ◽  
Cellular Origin

In the last decade, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in in vivo imaging has attempted to demonstrate the presence of neuroinflammatory reactions by measuring the 18 kDa translocator protein (TSPO) expression in many diseases of the central nervous system. We focus on two pathological conditions for which neuropathological studies have shown the presence of neuroinflammation, which translates in opposite in vivo expression of TSPO. Alzheimer’s disease has been the most widely assessed with more than forty preclinical and clinical studies, showing overall that TSPO is upregulated in this condition, despite differences in the topography of this increase, its time-course and the associated cell types. In the case of schizophrenia, a reduction of TSPO has instead been observed, though the evidence remains scarce and contradictory. This review focuses on the key characteristics of TSPO as a biomarker of neuroinflammation in vivo, namely, on the cellular origin of the variations in its expression, on its possible biological/pathological role and on its variations across disease phases.

scholarly journals Fluorescence-activated cell sorting to reveal the cell origin of radioligand binding

2019 ◽  
Vol 40 (6) ◽  
pp. 1242-1255 ◽  
Author(s):  
Benjamin B Tournier ◽  
Stergios Tsartsalis ◽  
Kelly Ceyzériat ◽  
Zadith Medina ◽  
Ben H Fraser ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Sorting ◽  
Radioligand Binding ◽  
Single Photon ◽  
Photon Emission ◽  
Cell Types ◽  
Translocator Protein ◽  
Emission Computed Tomography ◽  
Fluorescence Activated Cell Sorting

Many studies have explored the role of TSPO (18 kDa translocator protein) as a marker of neuroinflammation using single-photon emission computed tomography (SPECT) or positron emission tomography (PET). In vivo imaging does not allow to determine the cells in which TSPO is altered. We propose a methodology based on fluorescence-activated cell sorting to sort different cell types of radioligand-treated tissues. We compared left/right hippocampus of rats in response to a unilateral injection of lipopolysaccharide (LPS), ciliary neurotrophic factor (CNTF) or saline. We finally applied this methodology in human samples (Alzheimer's disease patients and controls). Our data show that the pattern of TSPO overexpression differs across animal models of acute neuroinflammation. LPS induces a microglial expansion and an increase in microglial TSPO binding. CNTF is associated with an increase in TSPO binding in microglia and astrocytes in association with an increase in the number of microglial binding sites per cell. In humans, we show that the increase in CLINDE binding in Alzheimer's disease concerns microglia and astrocytes in the presence of a microglial expansion. Thus, the cellular basis of TSPO overexpression is condition dependent, and alterations in TSPO binding found in PET/SPECT imaging studies cannot be attributed to particular cell types indiscriminately.

scholarly journals Astrocytic TSPO Upregulation Appears Before Microglial TSPO in Alzheimer’s Disease

2020 ◽  
Vol 77 (3) ◽  
pp. 1043-1056 ◽  
Author(s):  
Benjamin B. Tournier ◽  
Stergios Tsartsalis ◽  
Kelly Ceyzériat ◽  
Ben H. Fraser ◽  
Marie-Claude Grégoire ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Binding Sites ◽  
Temporal Cortex ◽  
Population Expansion ◽  
Cell Types ◽  
Translocator Protein ◽  
Cellular Origin

Background: In vivo PET/SPECT imaging of neuroinflammation is primarily based on the estimation of the 18 kDa-translocator-protein (TSPO). However, TSPO is expressed by different cell types which complicates the interpretation. Objective: The present study evaluates the cellular origin of TSPO alterations in Alzheimer’s disease (AD). Methods: The TSPO cell origin was evaluated by combining radioactive imaging approaches using the TSPO radiotracer [125I]CLINDE and fluorescence-activated cell sorting, in a rat model of AD (TgF344-AD) and in AD subjects. Results: In the hippocampus of TgF344-AD rats, TSPO overexpression not only concerns glial cells but the increase is visible at 12 and 24 months in astrocytes and only at 24 months in microglia. In the temporal cortex of AD subjects, TSPO upregulation involved only glial cells. However, the mechanism of this upregulation appears different with an increase in the number of TSPO binding sites per cell without cell proliferation in the rat, and a microglial cell population expansion with a constant number of binding sites per cell in human AD. Conclusion: These data indicate an earlier astrocyte intervention than microglia and that TSPO in AD probably is an exclusive marker of glial activity without interference from other TSPO-expressing cells. This observation indicates that the interpretation of TSPO imaging depends on the stage of the pathology, and highlights the particular role of astrocytes.

scholarly journals Brain Imaging of Nicotinic Receptors in Alzheimer's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Jin Wu ◽  
Masatomo Ishikawa ◽  
Jichun Zhang ◽  
Kenji Hashimoto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
The Brain

Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels which are widely distributed in the human brain. Several lines of evidence suggest that two major subtypes (α4β2 and α7) of nAChRs play an important role in the pathophysiology of Alzheimer's disease (AD). Postmortem studies demonstrated alterations in the density of these subtypes of nAChRs in the brain of patients with AD. Currently, nAChRs are one of the most attractive therapeutic targets for AD. Therefore, several researchers have made an effort to develop novel radioligands that can be used to study quantitatively the distribution of these two subtypes in the human brain with positron emission tomography (PET) and single-photon emission computed tomography (SPECT). In this paper, we discuss the current topics onin vivoimaging of two subtypes of nAChRs in the brain of patients with AD.

scholarly journals Efficacy and Limitations of rCBF-SPECT in the Diagnosis of Alzheimer’s Disease With Amyloid-PET

2019 ◽  
Vol 34 (5) ◽  
pp. 314-321
Author(s):  
Miwako Takahashi ◽  
Tomoko Tada ◽  
Tomomi Nakamura ◽  
Keitaro Koyama ◽  
Toshimitsu Momose
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Amyloid Pet ◽  
Clinical Dementia Rating ◽  
Positron Emission ◽  
Rcbf Spect

This study aimed to assess efficacy and limitations of regional cerebral blood flow imaging using single-photon emission computed tomography (rCBF-SPECT) in the diagnosis of Alzheimer’s disease (AD) with amyloid-positron emission tomography (amyloid-PET). Thirteen patients, who underwent both rCBF-SPECT and amyloid-PET after clinical diagnosis of AD or mild cognitive impairment, were retrospectively identified. The rCBF-SPECTs were classified into 4 grades, from typical AD pattern to no AD pattern of hypoperfusion; amyloid-beta (Aβ) positivity was assessed by amyloid-PET. Four patients were categorized into a typical AD pattern on rCBF-SPECT, and all were Aβ+. The other 9 patients did not exhibit a typical AD pattern; however, 4 were Aβ+. The Mini-Mental State Examination score and Clinical Dementia Rating scale were not significantly different between Aβ+ and Aβ– patients. A typical AD pattern on rCBF-SPECT can reflect Aβ+; however, if not, rCBF-SPECT has a limitation to predict amyloid pathology.

scholarly journals The Use of [99mTc]-HM-PAO in the Diagnosis of Primary Degenerative Dementia

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S123-S126 ◽  
Author(s):  
H. J. Testa ◽  
J. S. Snowden ◽  
D. Neary ◽  
R. A. Shields ◽  
A. W. I. Burjan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Frontal Lobe ◽  
Single Photon ◽  
Photon Emission ◽  
Cerebral Atrophy ◽  
Emission Computed Tomography ◽  
Clinical Value ◽  
Diagnosis Of Dementia

The clinical value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia due to cerebral atrophy was evaluated by comparing the pattern of distribution [99mTc]–HM-PAO in three dementing conditions. Imaging was carried out in 26 patients with suspected Alzheimer's disease, 14 with dementia of the frontal-lobe type, and 13 with progressive supranuclear palsy. Images were evaluated and reported without knowledge of clinical diagnosis with respect to regions of reduced uptake of tracer. Reduced uptake in the posterior cerebral hemispheres was characteristic of Alzheimer's disease, while selective anterior hemisphere abnormalities characterized both dementia of the frontal-lobe type and progressive supranuclear palsy. The latter conditions could be distinguished on the basis of the appearance of integrity of the rim of the frontal cortex. The technique has an important role in the differentiation of degenerative dementias.

scholarly journals Case Report: Usefulness of Biomarkers for Alzheimer's Disease in Two Cases With Very-Late-Onset Schizophrenia-Like Psychosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuto Satake ◽  
Hideki Kanemoto ◽  
Kenji Yoshiyama ◽  
Ryoko Nakahama ◽  
Keiko Matsunaga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Psychotic Disorders ◽  
Late Onset ◽  
Single Photon ◽  
Photon Emission ◽  
Brain Magnetic Resonance Imaging ◽  
Later Life ◽  
Emission Computed Tomography ◽  
Amyloid Pet

The association between primary psychotic disorders emerging in later life and neurodegenerative diseases, including Alzheimer's disease (AD), is controversial. We present two female non-demented cases of psychosis with onset above the age of 60 years. Cases 1 and 2 were aged was 68 and 81 years, respectively. They suffered from persecutory delusions and scored 28 on the Mini-Mental State Examination (MMSE) at the first examination. Although detailed neuropsychological tests detected amnesia, they had preserved daily life function. Brain magnetic resonance imaging, N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) single-photon emission computed tomography, and cardiac [123I]-metaiodobenzylguanidine (123I-MIBG) scintigraphy showed no specific abnormalities in either case. We diagnosed them with very-late-onset schizophrenia-like psychosis (VLOSLP) because there was no evidence that their psychoses were derived from organic diseases or affective disorders. Upon close inspection, the AD biomarkers, cerebrospinal fluid (CSF) testing and Florbetapir F 18 positron emission tomography (PET), were positive in Case 1 and negative in Case 2. Case 1 scored 25 1 year later and 23 2 years later on the MMSE and was finally diagnosed as AD dementia. These two cases suggest that some clinically diagnosed VLOSLPs may be a prodromal AD. Although VLOSLP is a disease entity supposed to be a primary psychotic disorder, some are probably secondary psychosis with insidious neurodegeneration. Advanced biomarkers such as amyloid PET and CSF may contribute to the detection of secondary psychosis from clinically diagnosed VLOSLP.

scholarly journals Novel PET/SPECT Probes for Imaging of Tau in Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hiroyuki Watanabe ◽  
Masahiro Ono ◽  
Hideo Saji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Current State ◽  
Positron Emission ◽  
Number Of Patients ◽  
State Of Research ◽  
Presymptomatic Diagnosis

As the world’s population ages, the number of patients with Alzheimer’s disease (AD) is predicted to increase rapidly. The presence of neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau protein, is one of the neuropathological hallmarks of AD brain. Since the presence of NFTs is well correlated with neurodegeneration and cognitive decline in AD, imaging of tau using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) is useful for presymptomatic diagnosis and monitoring of the progression of AD. Therefore, novel PET/SPECT probes for the imaging of tau have been developed. More recently, several probes were tested clinically and evaluated for their utility. This paper reviews the current state of research on the development and evaluation of PET/SPECT probes for the imaging of tau in AD brain.

Vascular risk factors and the relationships between cognitive impairment and hypoperfusion in late-onset Alzheimer’s disease

2018 ◽  
Vol 30 (6) ◽  
pp. 350-358 ◽  
Author(s):  
Michio Takahashi ◽  
Yasunori Oda ◽  
Koichi Sato ◽  
Yukihiko Shirayama
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Single Photon ◽  
Photon Emission ◽  
Disease Assessment ◽  
Emission Computed Tomography ◽  
Vascular Risk ◽  
Risk Patients

AbstractObjectiveOur recent single-photon emission computed tomography (SPECT) study of patients with late-onset Alzheimer’s disease (AD) revealed that regional cerebral blood flow (rCBF) was reduced in the frontal, temporal, and limbic lobes, and to a lesser degree in the parietal and occipital lobes. Moreover, these patients’ scores on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) were significantly correlated with rCBF in some gyri of the frontal, parietal, and limbic lobes. Our present study aimed to understand how vascular factors and metabolic disease influenced the relationship between rCBF and ADAS-cog scores.MethodsWe divided late-onset AD patients into two groups according to their Hachinski Ischemic Score (HIS), low vascular risk patients had values of ≤4 (n=25) and high vascular risk patients had scores ≥5 (n=15). We examined rCBF using brain perfusion SPECT data.ResultsThe degrees and patterns of reduced rCBF were largely similar between late-onset AD patients in both groups, regardless of HIS values. Cognitive function was significantly associated with rCBF among late-onset AD patients with low vascular risk (HIS≤4), but not among those with high vascular risk (HIS≥5). Furthermore, metabolic diseases, such as hypertension and diabetes mellitus, disrupted the relationships between hypoperfusion and cognitive impairments in late-onset AD patients.ConclusionFactors other than hypoperfusion, such as hypertension and diabetes mellitus, could be involved in the cognitive dysfunction of late-onset AD patients with high vascular risk.

scholarly journals Single Photon Emission Computed Tomography Using 99mTc-HM-PAO in the Routine Evaluation of Alzheimer's Disease

1991 ◽  
Vol 18 (1) ◽  
pp. 59-62 ◽  
Author(s):  
T.A. Hurwitz ◽  
W. Ammann ◽  
D. Chu ◽  
C. Clark ◽  
J. Holden ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Parietal Lobe ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Severe Dementia ◽  
Non Invasive ◽  
The One ◽  
Photon Emission Computed Tomography

ABSTRACT:Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia.

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