Upregulation of Cortical A2A Adenosine Receptors Is Reflected in Platelets of Patients with Alzheimer’s Disease

2021 ◽  
Vol 80 (3) ◽  
pp. 1105-1117
Author(s):  
Stefania Merighi ◽  
Enrica Battistello ◽  
Ilaria Casetta ◽  
Daniela Gragnaniello ◽  
Tino Emanuele Poloni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Entorhinal Cortex ◽  
Gray Matter ◽  
Receptor Subtypes ◽  
A2a Receptors ◽  
A2a Receptor ◽  
Significant Difference ◽  
Frontal White Matter

Background: Alzheimer’s disease (AD) is a neurodegenerative pathology covering about 70%of all cases of dementia. Adenosine, a ubiquitous nucleoside, plays a key role in neurodegeneration, through interaction with four receptor subtypes. The A2A receptor is upregulated in peripheral blood cells of patients affected by Parkinson’s and Huntington’s diseases, reflecting the same alteration found in brain tissues. However, whether these changes are also present in AD pathology has not been determined. Objective: In this study we verified any significant difference between AD cases and controls in both brain and platelets and we evaluated whether peripheral A2A receptors may reflect the status of neuronal A2A receptors. Methods: We evaluated the expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, in postmortem AD patients and control subjects, through [3H]ZM 241385 binding experiments. The same analysis was performed in peripheral platelets from AD patients versus controls. Results: The expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, revealed a density (Bmax) of 174±29, 219±33, and 358±84 fmol/mg of proteins, respectively, in postmortem AD patients in comparison to 104±16, 103±19, and 121±20 fmol/mg of proteins in controls (p < 0.01). The same trend was observed in peripheral platelets from AD patients versus controls (Bmax of 214±17 versus 95±4 fmol/mg of proteins, respectively, p < 0.01). Conclusion: AD subjects show significantly higher A2A receptor density than controls. Values on platelets seem to correlate with those in the brain supporting a role for A2A receptor as a possible marker of AD pathology and drug target for novel therapies able to modify the progression of dementia.

scholarly journals Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Malo Gaubert ◽  
Catharina Lange ◽  
Antoine Garnier-Crussard ◽  
Theresa Köbe ◽  
Salma Bougacha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Glucose Metabolism ◽  
Corpus Callosum ◽  
Gray Matter ◽  
Fdg Pet ◽  
White Matter Hyperintensities ◽  
Gray Matter Volume ◽  
Matter Volume

Abstract Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. Methods In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. Results There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. Conclusions This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

IC-P-014: Differences of gray matter and white matter volume in Alzheimer's disease and subcortical ischemic vascular dementia

2010 ◽  
Vol 6 ◽  
pp. S10-S11 ◽  
Author(s):  
Dong Won Yang ◽  
Yun Jeong Hong ◽  
A.-Hyun Cho ◽  
Bora Yoon ◽  
Yong Soo Shim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Vascular Dementia ◽  
Gray Matter ◽  
White Matter Volume ◽  
Matter Volume

scholarly journals GERIATRIC TRAUMATIC BRAIN INJURY AND ALZHEIMER’S DISEASE SHARE SIMILAR PATTERNS OF WHITE MATTER DEGRADATION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S96-S96
Author(s):  
Andrei Irimia ◽  
Kenneth Rostowsky ◽  
Nikhil Chaudhari ◽  
Maria Calvillo ◽  
Sean Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Future Research ◽  
Post Injury ◽  
Significant Difference

Abstract Although mild traumatic brain injury (mTBI) and Alzheimer’s disease (AD) are associated with white matter (WM) degradation, the nature of these alterations and the outcomes of their comparison have not been elucidated. Diffusion tensor imaging (DTI) has been utilized in both conditions, and has uncovered decreases in the fractional anisotropy (FA) of the corpus callosum and cingulum bundle, compared to healthy control (HC) volunteers [1, 2]. Despite mTBI being a potential risk factor for AD, no systematic quantitative comparison has been drawn between their WM degradation patterns. Here we investigated WM FA differences using DTI and tract-based spatial statistics (TBSS) between age- and sex-matched adults: 33 chronic mTBI patients, 67 AD patients and 81 HC participants. T1-weighted magnetic resonance imaging (MRI) and DTI were acquired at 3T. mTBI patients were scanned acutely and ~6 months post-injury. FSL software was used for artefact correction, FA computation and TBSS implementation. Statistical comparison of WM FA patterns between mTBI and AD patients was achieved by two one-sided t tests (TOSTs) of statistical equivalence, with equivalence bounds defined where Cohen’s d &lt; 0.3. A significant difference was found between the FA means of mTBI vs. HC groups, and the AD vs. HC groups (p &lt; 0.01, corrected). Mean FA differences between mTBI and AD were statistically equivalent in the corpus callosum and in the inferior longitudinal fasciculus (p &lt; 0.05, corrected). Future research should focus on clarifying the similarities between mTBI and AD, potentially leading to novel hypotheses and improved AD diagnosis.

scholarly journals Adenosine A2A Receptor Antagonists Affects NMDA Glutamate Receptor Function. Potential to Address Neurodegeneration in Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1075 ◽  
Author(s):  
Rafael Franco ◽  
Rafael Rivas-Santisteban ◽  
Mireia Casanovas ◽  
Alejandro Lillo ◽  
Carlos A. Saura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptor ◽  
Expression System ◽  
Primary Cultures ◽  
Adenosine A2a Receptor ◽  
A2a Receptors ◽  
Adenosine A2a Receptor Antagonists ◽  
A2a Receptor ◽  
Adenosine A2a

(1) Background. N-methyl d-aspartate (NMDA) ionotropic glutamate receptor (NMDAR), which is one of the main targets to combat Alzheimer’s disease (AD), is expressed in both neurons and glial cells. The aim of this paper was to assess whether the adenosine A2A receptor (A2AR), which is a target in neurodegeneration, may affect NMDAR functionality. (2) Methods. Immuno-histo/cytochemical, biophysical, biochemical and signaling assays were performed in a heterologous cell expression system and in primary cultures of neurons and microglia (resting and activated) from control and the APPSw,Ind transgenic mice. (3) Results. On the one hand, NMDA and A2A receptors were able to physically interact forming complexes, mainly in microglia. Furthermore, the amount of complexes was markedly enhanced in activated microglia. On the other hand, the interaction resulted in a novel functional entity that displayed a cross-antagonism, that could be useful to prevent the exacerbation of NMDAR function by using A2AR antagonists. Interestingly, the amount of complexes was markedly higher in the hippocampal cells from the APPSw,Ind than from the control mice. In neurons, the number of complexes was lesser, probably due to NMDAR not interacting with the A2AR. However, the activation of the A2AR receptors resulted in higher NMDAR functionality in neurons, probably by indirect mechanisms. (4) Conclusions. A2AR antagonists such as istradefylline, which is already approved for Parkinson’s disease (Nouriast® in Japan and Nourianz® in the US), have potential to afford neuroprotection in AD in a synergistic-like fashion. i.e., via both neurons and microglia.

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