scholarly journals Early compensatory responses against neuronal injury: A new therapeutic window of opportunity for Alzheimer's Disease?

2018 ◽  
Vol 25 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Sara Merlo ◽  
Simona Federica Spampinato ◽  
Maria Angela Sortino
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Injury ◽  
Therapeutic Window ◽  
Window Of Opportunity ◽  
Compensatory Responses

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.

Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer’s Disease

2019 ◽  
Vol 19 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Timo Grimmer ◽  
Oliver Goldhardt ◽  
Igor Yakushev ◽  
Marion Ortner ◽  
Christian Sorg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Pittsburgh Compound B ◽  
Positron Emission ◽  
Amyloid Load ◽  
Alzheimer’S Pathology

Background: Neprilysin (NEP) cleaves amyloid-β 1–42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated. Methods: Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer’s disease patients. Results: CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET. Conclusions: Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer’s pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.

Cerebrospinal Fluid Levels of a 20–22 kDa NH2 Fragment of Human Tau Provide a Novel Neuronal Injury Biomarker in Alzheimer's Disease and Other Dementias

2014 ◽  
Vol 42 (1) ◽  
pp. 211-226 ◽  
Author(s):  
Giuseppina Amadoro ◽  
Veronica Corsetti ◽  
Giulia Maria Sancesario ◽  
Adele Lubrano ◽  
Gaia Melchiorri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Neuronal Injury ◽  
Cerebrospinal Fluid Levels ◽  
Fluid Levels

scholarly journals Alpha-2 macroglobulin in Alzheimer’s disease: a marker of neuronal injury through the RCAN1 pathway

2016 ◽  
Vol 22 (1) ◽  
pp. 13-23 ◽  
Author(s):  
V R Varma ◽  
◽  
S Varma ◽  
Y An ◽  
T J Hohman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Injury

[P1-416]: CSF TOTAL TAU AS A BIOMARKER FOR NEURONAL INJURY IN ALZHEIMER's DISEASE: ALIGNING RATES OF CSF CHANGE WITH RATES OF HIPPOCAMPAL AND CORTICAL GRAY MATTER ATROPHY

2017 ◽  
Vol 13 (7S_Part_8) ◽  
pp. P436-P436
Author(s):  
James D. Doecke ◽  
Qiao-Xin Li ◽  
Pierrick Bourgeat ◽  
Christopher Fowler ◽  
Steven Collins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gray Matter ◽  
Neuronal Injury ◽  
Total Tau ◽  
Gray Matter Atrophy ◽  
Cortical Gray Matter

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.

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