The genetic analysis of a new trinucleotide repeat (D5S373) was carried out with a view to its application in both individual genetic profiling and human population genetics. In a screening analysis from seven world populations (n = 706) and after nucleotide sequence analysis, up to nine alleles were found corresponding to 8-13 repetitions of a TAA motif. This analysis shows He values ranging between 0.689-0.762. D5S373 reveals interpopulational variability which leads to specific frequency profiles in the major human groups, with alleles 8, 11, l2, and 13 being particularly informative, which suggests the that this marker may be of interest in the biological study of human populations.
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http://dx.doi.org/10.1002/ajhb.10028 | DOI Listing |
Alzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.
Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.
Background: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
View Article and Find Full Text PDFBackground: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
View Article and Find Full Text PDFBackground: Understanding the fundamental differences between the human and pre-human brain is a prerequisite for designing meaningful models and therapies for AD. Expressed CHRFAM7A, a human restricted gene with carrier frequency of 75% in the human population predicts profound translational significance.
Method: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples (ROSMAP).
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