A Comparative Study of Plasma Biomarkers of Neurodegeneration in Rhesus Monkeys (Macaca mulatta) and Baboons (Papio anubis)

Clinically Relevant Biomarkers of Alzheimer’s Disease Are Associated with Age and Cortical Atrophy in Chimpanzees (Pan troglodytes)

This work believes this is the first evidence demonstrating an association between these clinically relevant biomarkers of Alzheimer’s disease and phenotypes of brain aging in nonhuman primates, underscoring their importance as models of aging and neurodegenerative disease.

Relative importance of blood-based biomarkers for Alzheimer’s disease-specific neurodegeneration and cognitive decline

A stratified approach based on amyloid status is essential for the optimal application of blood-based biomarkers in monitoring disease progression and evaluating therapeutic efficacy in future clinical trials and precision medicine.

A New Frontier in CWD Detection: Antemortem Plasma Biomarkers and Behavioral Profiling in Transgenic Mouse Models

Targeted proteomics of postmortem human brain reveals neurobiologic heterogeneity in Alzheimer’s disease using NULISA technology

African Green Monkey Cerebrospinal Fluid miRNome Captures Conserved miRNAs Relevant to Human Neurodegenerative Disease

Background The African green monkey (AGM) is increasingly used as a model for early-stage Alzheimer’s disease (AD), with cerebrospinal fluid (CSF) targeted for biomarker discovery and longitudinal disease monitoring of shifts in the central nervous system. MicroRNAs (miRNAs) are particularly informative indicators of early neuropathological change. Despite the complementary value of an early-stage disease model and a molecular marker capable of capturing early change, the miRNA composition (miRNome) of AGM remains undefined. We established the AGM CSF miRNome from antemortem samples using miRNA sequencing and a qRT-PCR-based array. We also developed a hierarchical annotation pipeline to classify miRNAs as either family-conserved or unclassified and to assess sequence alignment across humans and other species. Results We used untargeted miRNA sequencing to characterize the AGM CSF miRNome and identified 205 miRNAs that could be classified into three family-conserved categories: canonical, noncanonical, and 3′-terminal variants. Of these, 150 were also detected using a human-targeted qRT-PCR array, providing independent support for the sequence-derived miRNome. Sequencing abundance and qRT-PCR array Ct values showed significant cross-platform concordance overall, although concordance was lower for 3′-terminal isomiRs than for canonical miRNAs. Comparison with human GTEx tissue-expression data indicated that several human homologs of AGM CSF miRNAs exhibited brain-preferential expression. Notably, predicted targets of many of these miRNAs were enriched for pathways implicated in neurodegenerative disease. Finally, we identified 20 unclassified candidates that could not be assigned to established miRNA families, two of which we propose as putatively novel miRNAs. Conclusion The AGM CSF miRNome is substantially conserved with the human miRNome but also contains 3′-terminal isomiRs and unclassified miRNA candidates. AGM CSF contains miRNAs homologous to human miRNAs associated with AD and other neuropathologies, highlighting the translational potential of this model. However, our study also reveals challenges related to species-specific sequence variation and reduced cross-platform concordance for isomiRs. Thus, comparative studies will be needed to validate the functional and biomarker relevance of these miRNAs across species. More generally, this initial miRNome provides a reference resource for future studies of miRNAs in AGM across disease-related, physiological, experimental, and evolutionary contexts.

From Animal Models to At-Home Monitoring: The Translational Potential of Sleep Spindles as Non-invasive Biomarkers for Alzheimer's Disease

Alzheimer's disease (AD) is becoming more common and putting serious pressure on global health. Current Amyloid-β (Aβ) deposition and tau protein hyperphosphorylation are two main biomarkers of AD. Clinical diagnostic approaches depend on invasive detection of amyloid-β (Aβ) deposition and tau protein hyperphosphorylation through cerebrospinal fluid (CSF) analysis, positron emission tomography (PET) imaging or blood-based biomarker (BBM) testing. Evidence showed by recent studies have identified that slow-wave-sleep spindle coupling as potential non-invasive biomarkers of neurodegeneration for AD patients. Yet, the causality between spindle disruption and cognitive decline remains unknown. This paper examines the evidences from human, rodent models, and nonhuman primate (NHP) models of recent studies. This study presents how slow wave-spindle coupling reflects prefrontal-hippocampal, thalamocortical function. And it evaluates the contributions of NHPs researches for understanding the causal mechanisms. The findings provide supportive evidence that slow-wave-spindle activity is a reliable marker of thalamocortical integrity and prefrontal-hippocampal function correlating with cognitive decline for AD. Study shows the non-rapid eye movement (NREM) spindle and slow oscillation (SO) activity are predictive and non-invasive biomarkers for AD. The disruption of spindle-SO coupling is associated with Aβ deposits of AD. This predictive biomarker of AD points toward future directions for early detection and clinical interventions. These findings enable standardized predictive detection, home-based electroencephalography (EEG) monitoring and closed-loop stimulation techniques that could strengthen the clinical translation.