scholarly journals Therapeutic window of dopamine D2/3 receptor occupancy to treat psychosis in Alzheimer’s disease

Brain ◽  
2017 ◽  
Vol 140 (4) ◽  
pp. 1117-1127 ◽  
Author(s):  
Suzanne Reeves ◽  
Emma McLachlan ◽  
Julie Bertrand ◽  
Fabrizia D’Antonio ◽  
Stuart Brownings ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Receptor Occupancy ◽  
Therapeutic Window ◽  
Dopamine D2

Biomarkers and Tools for Predicting Alzheimer’s Disease at the Preclinical Stage

2021 ◽  
Vol 19 ◽  
Author(s):  
Tao-Ran Li ◽  
Qin Yang ◽  
Xiaochen Hu ◽  
Ying Han
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Communication ◽  
High Sensitivity ◽  
Screening Tools ◽  
Therapeutic Window ◽  
Subjective Cognitive Decline ◽  
Preclinical Stage ◽  
Functional Changes ◽  
Preclinical Ad

: Alzheimer’s disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Over the past decade, a string of disappointing clinical trial results has forced us to shift our focus to the preclinical stage of AD, which represents the most promising therapeutic window. However, the accurate diagnosis of preclinical AD requires the presence of brain β-amyloid deposition determined by cerebrospinal fluid or amyloid-positron emission tomography, significantly limiting routine screening and diagnosis in non-tertiary hospital settings. Thus, an easily accessible marker or tool with high sensitivity and specificity is highly needed. Recently, it has been discovered that individuals in the late stage of preclinical AD may not be truly “asymptomatic” in that they may have already developed subtle or subjective cognitive decline. In addition, advances in blood-derived biomarker studies have also allowed detection of pathologic changes in preclinical AD. Exosomes, as cell-to-cell communication messengers, can reflect the functional changes of their source cell. Methodological advances have made it possible to extract brain-derived exosomes from peripheral blood, making exosomes an emerging biomarker carrier and liquid biopsy tool for preclinical AD. The eye and its associated structures have rich sensory-motor innervation. In this regard, studies have indicated that they may also provide reliable markers. Here, our report covers the current state of knowledge of neuropsychological and eye tests as screening tools for preclinical AD and assesses the value of blood and brain-derived exosomes as carriers of biomarkers in conjunction with the current diagnostic paradigm.

Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older Patients with Schizophrenia: A Pilot PET Study

2014 ◽  
Vol 22 (10) ◽  
pp. 1007-1016 ◽  
Author(s):  
Hiroyuki Uchida ◽  
Takefumi Suzuki ◽  
Ariel Graff-Guerrero ◽  
Benoit H. Mulsant ◽  
Bruce G. Pollock ◽  
...  
Keyword(s):  
Older Patients ◽  
Receptor Occupancy ◽  
Striatal Dopamine ◽  
Therapeutic Window ◽  
Dopamine D2

Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older Patients With Schizophrenia

2012 ◽  
pp. 1 ◽  
Author(s):  
Hiroyuki Uchida ◽  
Takefumi Suzuki ◽  
Ariel Graff-Guerrero ◽  
Benoit H. Mulsant ◽  
Bruce G. Pollock ◽  
...  
Keyword(s):  
Older Patients ◽  
Receptor Occupancy ◽  
Striatal Dopamine ◽  
Therapeutic Window ◽  
Dopamine D2

Targeting Post-Translational Remodeling of Ryanodine Receptor: A New Track for Alzheimer's Disease Therapy?

2020 ◽  
Vol 17 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Mounia Chami ◽  
Frédéric Checler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Complex Structure ◽  
Ryanodine Receptors ◽  
Therapeutic Window ◽  
Signaling Cascade ◽  
Macromolecular Complex ◽  
Macromolecular Complexes

Pathologic calcium (Ca2+) signaling linked to Alzheimer’s Disease (AD) involves the intracellular Ca2+ release channels/ryanodine receptors (RyRs). RyRs are macromolecular complexes where the protein-protein interactions between RyRs and several regulatory proteins impact the channel function. Pharmacological and genetic approaches link the destabilization of RyRs macromolecular complexes to several human pathologies including brain disorders. In this review, we discuss our recent data, which demonstrated that enhanced neuronal RyR2-mediated Ca2+ leak in AD is associated with posttranslational modifications (hyperphosphorylation, oxidation, and nitrosylation) leading to RyR2 macromolecular complex remodeling, and dissociation of the stabilizing protein Calstabin2 from the channel. We describe RyR macromolecular complex structure and discuss the molecular mechanisms and signaling cascade underlying neuronal RyR2 remodeling in AD. We provide evidence linking RyR2 dysfunction with β-adrenergic signaling cascade that is altered in AD. RyR2 remodeling in AD leads to histopathological lesions, alteration of synaptic plasticity, learning and memory deficits. Targeting RyR macromolecular complex remodeling should be considered as a new therapeutic window to treat/or prevent AD setting and/or progression.

Increased galanin receptor occupancy in Alzheimer’s disease

2004 ◽  
Vol 25 (10) ◽  
pp. 1309-1314 ◽  
Author(s):  
Pamela J. McMillan ◽  
Elaine Peskind ◽  
Murray A. Raskind ◽  
James B. Leverenz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Receptor Occupancy ◽  
Galanin Receptor

scholarly journals Synchronous nonmonotonic changes in functional connectivity and white matter integrity in a rat model of sporadic Alzheimer’s disease

2020 ◽  
Author(s):  
Catarina Tristão Pereira ◽  
Yujian Diao ◽  
Ting Yin ◽  
Analina R da Silva ◽  
Bernard Lanz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Functional Connectivity ◽  
Structure And Function ◽  
Acute Injury ◽  
Therapeutic Window ◽  
Brain Glucose ◽  
And Function ◽  
Glucose Hypometabolism

AbstractBrain glucose hypometabolism has been singled out as an important contributor and possibly main trigger to Alzheimer’s disease (AD). Intracerebroventricular injections of streptozotocin (icv-STZ) cause brain glucose hypometabolism without systemic diabetes. Here, a first-time longitudinal study of brain glucose metabolism, functional connectivity and white matter microstructure was performed in icv-STZ rats using PET and MRI. Histological markers of pathology were tested at an advanced stage of disease. STZ rats exhibited altered functional connectivity and intra-axonal damage and demyelination in brain regions typical of AD, in a temporal pattern of acute injury, transient recovery/compensation and chronic degeneration. In the context of sustained glucose hypometabolism, these nonmonotonic trends – also reported in behavioral studies of this animal model as well as in human AD – suggest a compensatory mechanism, possibly recruiting ketone bodies, that allows a partial and temporary repair of brain structure and function. The early acute phase could thus become a valuable therapeutic window to strengthen the recovery phase and prevent or delay chronic degeneration, to be considered both in preclinical and clinical studies of AD. In conclusion, this work reveals the consequences of brain insulin resistance on structure and function, highlights signature nonmonotonic trajectories in their evolution and proposes potent MRI-derived biomarkers translatable to human AD and diabetic populations.

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