scholarly journals Identification of retinoblastoma binding protein 7 (Rbbp7) as a mediator against tau acetylation and subsequent neuronal loss in Alzheimer’s disease and related tauopathies

2021 ◽  
Author(s):  
Nikhil Dave ◽  
Austin S. Vural ◽  
Ignazio S. Piras ◽  
Wendy Winslow ◽  
Likith Surendra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Death ◽  
Binding Protein ◽  
Tau Phosphorylation ◽  
Neuritic Plaque ◽  
Post Mortem ◽  
Post Mortem Brain ◽  
Tau Acetylation

AbstractEvidence indicates that tau hyper-phosphorylation and subsequent neurofibrillary tangle formation contribute to the extensive neuronal death in Alzheimer’s disease (AD) and related tauopathies. Recent work has identified that increased tau acetylation can promote tau phosphorylation. Tau acetylation occurs at lysine 280 resulting from increased expression of the lysine acetyltransferase p300. The exact upstream mechanisms mediating p300 expression remain elusive. Additional work highlights the role of the epigenome in tau pathogenesis, suggesting that dysregulation of epigenetic proteins may contribute to acetylation and hyper-phosphorylation of tau. Here, we identify and focus on the histone-binding subunit of the Nucleosome Remodeling and Deacetylase (NuRD) complex: Retinoblastoma-Binding Protein 7 (Rbbp7). Rbbp7 chaperones chromatin remodeling proteins to their nuclear histone substrates, including histone acetylases and deacetylases. Notably, Rbbp7 binds to p300, suggesting that it may play a role in modulating tau acetylation. We interrogated Rbbp7 in post-mortem brain tissue, cell lines and mouse models of AD. We found reduced Rbbp7 mRNA expression in AD cases, a significant negative correlation with CERAD (neuritic plaque density) and Braak Staging (pathogenic tau inclusions) and a significant positive correlation with post-mortem brain weight. We also found a neuron-specific downregulation of Rbbp7 mRNA in AD patients. Rbbp7 protein levels were significantly decreased in 3xTg-AD and PS19 mice compared to NonTg, but no decreases were found in APP/PS1 mice that lack tau pathology. In vitro, Rbbp7 overexpression rescued TauP301L-induced cytotoxicity in immortalized hippocampal cells and primary cortical neurons. In vivo, hippocampal Rbbp7 overexpression rescued neuronal death in the CA1 of PS19 mice. Mechanistically, we found that increased Rbbp7 reduced p300 levels, tau acetylation at lysine 280 and tau phosphorylation at AT8 and AT100 sites. Collectively, these data identify a novel role of Rbbp7, protecting against tau-related pathologies, and highlight its potential as a therapeutic target in AD and related tauopathies.

P1-155: Post-Mortem Brain Tissue Characterisation of Inflammatory and Pathological Hallmarks of Alzheimer’s Disease During Disease Progression

2016 ◽  
Vol 12 ◽  
pp. P462-P462
Author(s):  
Martina M. Hughes ◽  
Beatriz G. Perez-Nievas ◽  
Claire Troakes ◽  
Michael Perkinton ◽  
Diane P. Hanger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Brain Tissue ◽  
Post Mortem ◽  
Tissue Characterisation ◽  
Post Mortem Brain

scholarly journals Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer’s Disease Patients

2018 ◽  
Vol 12 ◽  
Author(s):  
Simin Mahinrad ◽  
Marjolein Bulk ◽  
Isabelle van der Velpen ◽  
Ahmed Mahfouz ◽  
Willeke van Roon-Mom ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Brain Tissue ◽  
Natriuretic Peptides ◽  
Post Mortem ◽  
Post Mortem Brain

Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer’s disease

2020 ◽  
Vol 191 ◽  
pp. 111352
Author(s):  
Adriane D. Henriques ◽  
Wilcelly Machado-Silva ◽  
Renata E.P. Leite ◽  
Claudia K. Suemoto ◽  
Kátia R.M. Leite ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Post Mortem ◽  
Genome Wide ◽  
Post Mortem Brain

scholarly journals Molecular signatures in post-mortem brain tissue of younger individuals at high risk for Alzheimer's disease as based on APOE genotype

2010 ◽  
Vol 16 (8) ◽  
pp. 836-847 ◽  
Author(s):  
C Conejero-Goldberg ◽  
T M Hyde ◽  
S Chen ◽  
U Dreses-Werringloer ◽  
M M Herman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Risk ◽  
Brain Tissue ◽  
Apoe Genotype ◽  
Molecular Signatures ◽  
Post Mortem ◽  
Post Mortem Brain

scholarly journals Platelet phosphorylated TDP-43: An exploratory study for a peripheral surrogate biomarker development for Alzheimer’s disease

2017 ◽  
Author(s):  
Rodger Wilhite ◽  
Jessica Sage ◽  
Abdurrahman Bouzid ◽  
Tyler Primavera ◽  
Abdulbaki Agbas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Signs ◽  
Brain Regions ◽  
Post Mortem ◽  
Disease Prognosis ◽  
Post Mortem Brain ◽  
And Control ◽  
Lateral Sclerosis

AbstractAim: Alzheimer’s disease (AD) and other forms of dementia create a non-curable disease population in World’s societies. To develop a blood-based biomarker is important so that the remedial or disease-altering therapeutic intervention for AD patients would be available at the early stage. Materials & Methods: TDP-43 levels were analyzed in post-mortem brain tissue and platelets of AD and control subjects. Results: We observed an increased TDP-43 (<60%) in post-mortem AD brain regions and similar trends were also observed in patient’s platelets. Conclusion: Platelet TDP-43 could be used as a surrogate biomarker that is measurable, reproducible, and sensitive for screening the patients with some early clinical signs of AD and can be used to monitor disease prognosis.Lay abstractIn this study, we explore to identify an Alzheimer’s disease-selective phospho-specific antibody that recognizes the diseased form of TDP-43 protein in patient’s blood-derived platelets. Our results suggest that selective anti-phosphorylated TDP-43 antibody discriminates Alzheimer’s disease from non-demented controls and patients with amyotrophic lateral sclerosis. Therefore, platelet screening with a selective antibody could potentially be a useful tool for diagnostic purposes for Alzheimer’s disease.

Altered expression of tau exon 10, clk2 and htra2-ß in post mortem brain of patients with Alzheimer’s disease

2004 ◽  
Vol 36 (05) ◽  
Author(s):  
D Glatz ◽  
F Berendt ◽  
F Faltraco ◽  
AM Hartmann ◽  
H Hampel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Post Mortem ◽  
Altered Expression ◽  
Post Mortem Brain ◽  
Exon 10

Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of Alzheimer’s disease

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Simone Eggert ◽  
Stefan Kins ◽  
Kristina Endres ◽  
Tanja Brigadski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Death ◽  
Common Features ◽  
Interaction Partners ◽  
The Central Nervous System ◽  
Bdnf Signaling ◽  
The Common ◽  
The Brain

Abstract Brain-derived neurotrophic factor (BDNF) is an important modulator for a variety of functions in the central nervous system (CNS). A wealth of evidence, such as reduced mRNA and protein level in the brain, cerebrospinal fluid (CSF), and blood samples of Alzheimer’s disease (AD) patients implicates a crucial role of BDNF in the progression of this disease. Especially, processing and subcellular localization of BDNF and its receptors TrkB and p75 are critical determinants for survival and death in neuronal cells. Similarly, the amyloid precursor protein (APP), a key player in Alzheimer’s disease, and its cleavage fragments sAPPα and Aβ are known for their respective roles in neuroprotection and neuronal death. Common features of APP- and BDNF-signaling indicate a causal relationship in their mode of action. However, the interconnections of APP- and BDNF-signaling are not well understood. Therefore, we here discuss dimerization properties, localization, processing by α- and γ-secretase, relevance of the common interaction partners TrkB, p75, sorLA, and sortilin as well as shared signaling pathways of BDNF and sAPPα.

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