scholarly journals Identification of novel Alzheimer’s disease genes co-expressed with TREM2

2020 ◽  
Author(s):  
Joseph S. Reddy ◽  
Mariet Allen ◽  
Xue Wang ◽  
Joanna M. Biernacka ◽  
Brandon J. Coombes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Cells ◽  
Disease Genes ◽  
Exome Data ◽  
Sequencing Project ◽  
Novel Approach ◽  
Whole Exome ◽  
Therapeutic Development

AbstractBy analyzing whole-exome data from the Alzheimer’s disease sequencing project (ADSP), we identify a set of 4 genes that show highly significant association with Alzheimer’s disease (AD). These genes were identified within a human TREM2 co-expression network using a novel approach wherein prioritized polygenic score analyses were performed sequentially to identify significant polygenic components. Two of the 4 genes (TREM2, RIN3) have previously been linked to AD and two (ATP8B4, IL17RA) are novel. Like TREM2, the 2 novel AD genes are selectively expressed in human microglial cells. The most significant variants in ATP8B4 and IL17RA are non-synonymous variants with strong effects comparable to the APOE ε4 and ε2 alleles. These protein-altering variants will provide unique opportunities to further explore the biological role of microglial cells in AD and help inform future immune modulatory therapeutic development for AD.

P4-044: THE GCAD CLOUD-BASED WORKFLOW FOR PROCESSING WHOLE EXOME AND WHOLE GENOME DATA FROM THE ALZHEIMER'S DISEASE SEQUENCING PROJECT

2006 ◽  
Vol 14 (7S_Part_27) ◽  
pp. P1450-P1450
Author(s):  
Prabhakaran Gangadharan ◽  
Yuk Yee Leung ◽  
Otto Valladares ◽  
Yi-Fan Chou ◽  
Amanda B. Kuzma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome ◽  
Sequencing Project ◽  
Genome Data ◽  
Whole Exome

scholarly journals O1-09-02: Whole Exome Sequencing of Late Onset Multiplex Families Identifies Rare Coding Variants in Known and Novel Alzheimer’s Disease Genes

2016 ◽  
Vol 12 ◽  
pp. P196-P197
Author(s):  
Holly N. Cukier ◽  
Brian W. Kunkle ◽  
Sophie Rolati ◽  
Patrice L. Whitehead ◽  
Jeffery M. Vance ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Late Onset ◽  
Disease Genes ◽  
Whole Exome ◽  
Multiplex Families ◽  
Coding Variants

scholarly journals Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Somayra S. A. Mamsa ◽  
Bruno P. Meloni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Aggregation ◽  
Amyloid Beta ◽  
Beneficial Effects ◽  
Therapeutic Development ◽  
Therapeutic Compounds ◽  
Tau Aggregation ◽  
Excitotoxic Cell Death

A substantial body of evidence indicates cationic, arginine-rich peptides (CARPs) are effective therapeutic compounds for a range of neurodegenerative pathologies, with beneficial effects including the reduction of excitotoxic cell death and mitochondrial dysfunction. CARPs, therefore, represent an emergent class of promising neurotherapeutics with multimodal mechanisms of action. Arginine itself is a known chaotrope, able to prevent misfolding and aggregation of proteins. The putative role of proteopathies in chronic neurodegenerative diseases such as Alzheimer’s disease (AD) warrants investigation into whether CARPs could also prevent the aggregation and cytotoxicity of amyloidogenic proteins, particularly amyloid-beta and tau. While monomeric arginine is well-established as an inhibitor of protein aggregation in solution, no studies have comprehensively discussed the anti-aggregatory properties of arginine and CARPs on proteins associated with neurodegenerative disease. Here, we review the structural, physicochemical, and self-associative properties of arginine and the guanidinium moiety, to explore the mechanisms underlying the modulation of protein aggregation by monomeric and multimeric arginine molecules. Arginine-rich peptide-based inhibitors of amyloid-beta and tau aggregation are discussed, as well as further modulatory roles which could reduce proteopathic cytotoxicity, in the context of therapeutic development for AD.

scholarly journals Role of Microglial Cells in Alzheimer’s Disease Tau Propagation

2019 ◽  
Vol 11 ◽  
Author(s):  
Ena Španić ◽  
Lea Langer Horvat ◽  
Patrick R. Hof ◽  
Goran Šimić
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Cells

scholarly journals Progression of Cognitive Impairment to Alzheimer’s Disease: Through the Lens of Salivary Extracellular Vesicles

2021 ◽  
Vol 16 ◽  
pp. 263310552110586
Author(s):  
Simran Rastogi ◽  
Komal Rani ◽  
Saroj Kumar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Screening Method ◽  
Extracellular Vesicle ◽  
Cognitively Impaired ◽  
Non Invasive ◽  
Novel Approach ◽  
Place Of Origin

The elusiveness encircling around the domain of cognition, its impairment, and the poor prognosis of Alzheimer’s disease has made early diagnosis a necessity. The noticeable symptoms in these conditions appear years later after the neuropathological changes occur in the brain. Exosomes, a small-sized extracellular vesicle facilitate intercellular communication of disease pathologies and their cargo can provide molecular information about its place of origin. The study titled “A novel approach to correlate the salivary exosomes and their protein cargo in the progression of cognitive impairment into Alzheimer’s disease” was an attempt toward understanding the role of salivary small-sized extracellular vesicular (EV’s) cargo in monitoring the progression. Outcomes of the study represent, that the salivary small-sized EV’s (ssEV’s) levels were higher in the cognitively impaired and Alzheimer’s diseased as well the differential expression of the protein in the cargo correlates well with the disease severity staging. Thus, it can help in the development of an early non-invasive screening method.

scholarly journals Whole-exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer's disease

2018 ◽  
Vol 44 (5) ◽  
pp. 506-521 ◽  
Author(s):  
T. Patel ◽  
K. J. Brookes ◽  
J. Turton ◽  
S. Chaudhury ◽  
T. Guetta-Baranes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome
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