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Fecal sampling is a non-invasive methodology for obtaining DNA for genetic studies in wild animals. The capuchin monkey, Sapajus nigritus and the invasive marmosets in Southeast Brazil, Callithrix jacchus , C. penicillata, and their hybrids, have been among the targets of these studies. The commercial kits for fecal DNA extraction from feces, still demand a high cost, and to circumvent this situation, homemade protocols can be used. Our objective was to test the protocols of Finger (2015) and Doyle & Doyle (1987) to extract fecal DNA from S. nigritus and Callithrix spp., evaluating their efficiency for PCR and the influence of collection time and storage method. Thirteen fecal samples were collected in Rio de Janeiro in different locations and periods. Three experiments were designed to test the protocols. In test 1, with samples collected in 2015, 2018, and 2019 preserved in 70% ethanol, no DNA was obtained with any protocol. The Finger protocol was also not successful in tests 2 and 3, with samples collected in 2023. The Doyle & Doyle protocol was efficient in tests 2 and 3, with extractions on the day of collection and up to a month of storage at -20°C. Callithrix fecal DNA generated an amplicon in the first PCR, whereas for S. nigritus , only in the second PCR, after dilution of the DNA and probable reduction of inhibitors. The Doyle & Doyle (1987) protocol was efficient for extracting fecal DNA of the species studied from fresh feces or from those stored for up to 30 days at -20°C.

The amyloid/tau/neurodegeneration (ATN) biomarker framework has greatly progressed the diagnosis and staging of Alzheimer's disease (AD). However, recent research highlights neuroinflammation as an equally critical factor in AD pathology across humans, rodents, and non‐human primates (NHPs). This review evaluates the combined use of ATN and neuroinflammatory biomarkers—such as glial fibrillary acidic protein (GFAP) (astrocytic marker) and triggering receptor expressed on myeloid cells 2 (TREM2)/ ionized calcium‐binding adapter molecule 1 (IBA‐1) (microglial markers)—in elucidating AD mechanisms, promoting early diagnosis, and shaping therapeutic strategies. It also summarizes the key features and translational potential of NHP models that closely mimic human AD pathology, highlighting the promising prospects of integrating these models with the ATN(X) biomarker system. These insights strengthen the link between biomarkers, NHP research, and clinical practice, opening new avenues for the early detection and treatment strategies of AD. Highlights Neuroinflammation biomarkers, including glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2)/sTREM2, and YKL‐40, show strong clinical potential in Alzheimer's disease (AD). Incorporating neuroinflammation biomarkers into the ATN(X) framework may enhance diagnostic precision. Advanced non‐human primate (NHP) models closely replicate human brain pathology, addressing key limitations of mouse models. Measuring ATN(X) biomarkers in NHPs may improve clinical translation and support early diagnosis of AD. Optimizing NHP models—including ApoE4 status, injection protocols, and gene‐editing approaches—is crucial for reproducibility and efficiency.

We previously reported that a unilateral dorsal column lesion (DCL) at the cervical C4 level primarily reduces inter‐horn resting‐state functional connectivity (rsFC) measured by functional Magnetic Resonance Imaging (fMRI) in segments below the lesion. This study compares changes in rsFC from fMRI with changes in local field potential (LFP) coherence over an extended post‐injury period. High‐resolution fMRI and LFP data were acquired bilaterally in healthy monkeys and at 3‐ and 6‐months post‐lesion. At 3 months post‐injury, tactile‐stimulus‐evoked LFP power in the dorsal horn was significantly weaker than in the healthy cord and non‐lesion side. LFP coherences increased on the lesion side for the dorsal‐to‐intermediate zone (D‐IGM) and dorsal‐to‐ventral (D‐V) pairs but decreased for the non‐lesion side D‐IGM. By 6 months, stimulus‐evoked LFP power on the lesion side remained low. LFP coherences between dorsal‐to‐dorsal (D‐D), ventral‐to‐ventral (V‐V), and D‐V pairs on both the lesion and non‐lesion sides were significantly reduced relative to the healthy cord. Low‐frequency (delta, theta, and alpha) D‐IGM coherences on the lesion side, and high‐frequency (beta and gamma) coherences on the non‐lesion side, were also significantly weakened. Across specific inter‐horn pairs and time points, changes in LFP coherences and rsFC measures were weakly correlated. Measurements of inter‐horn correlations two segments caudal to the lesion level at C7 revealed distance‐dependent intraspinal connectivity changes following DCL. Post‐mortem histology confirmed a complete DCL in most animals (7/9). The extent of the disruption of ascending sensory afferents, as assessed histologically, did not appear to correlate with the degree of LFP power reduction or rsFC changes at post‐injury time points. In summary, we observed temporally and spatially heterogeneous changes of fMRI correlations and LFP coherences within intraspinal circuits. fMRI rsFC and LFP coherences were not always concordant, with discrepancies depending on specific gray‐matter horns and intermediate‐zone pairs. Unilateral spinal cord injury in monkeys induces widespread and dynamic changes in resting‐state functional connectivity (rsFC), mirroring alterations in local field potential (LFP) coherence. Our findings reveal spatially and temporally complex intraspinal plasticity, supporting rsFC as a potential electrophysiologically grounded biomarker for monitoring spinal cord injury and recovery.

INTRODUCTION Vervets are non‐human primates that share high genetic homology with humans and develop amyloid beta (Aβ) pathology with aging. We expand current knowledge by examining Aβ pathology, aging, cognition, and biomarker proteomics. METHODS Amyloid immunoreactivity in the frontal cortex and temporal cortex/hippocampal regions from archived vervet brain samples ranging from young adulthood to old age was quantified. We also obtained cognitive scores, plasma samples, and cerebrospinal fluid (CSF) samples in additional animals. Plasma and CSF proteins were quantified with platforms utilizing human antibodies. RESULTS We found age‐related increases in Aβ deposition in both brain regions. Bioinformatic analyses assessed associations between biomarkers and age, sex, cognition, and CSF Aβ levels, revealing changes in proteins related to immune‐related inflammation, metabolism, and cellular processes. DISCUSSION Vervets are an effective model of aging and early‐stage Alzheimer's disease, and we provide translational biomarker data that both align with previous results in humans and provide a basis for future investigations. Highlights We found changes in immune and metabolic plasma biomarkers associated with age and cognition. Cerebrospinal fluid (CSF) biomarkers revealed changes in cell signaling indicative of adaptative processes. TNFRSF19 (TROY) and Artemin co‐localize with Alzheimer's disease pathology. Vervets are a relevant model for translational studies of early‐stage Alzheimer's disease.

INTRODUCTION Pathological accumulation of tau (pTau) contributes to various tauopathies, including Alzheimer's disease (AD), and correlates with cognitive decline. A rapid surge in tau‐targeted approaches via anti‐sense oligonucleotides, active/passive immunotherapies suggests that targeting p‐Tau is a viable strategy against tauopathies. METHOD We describe a multi‐species validation of our previously described Qß virus‐like particle (VLP)–based vaccine technology targeting phosphorylated tau on threonine 181 (pT181‐Qß). RESULTS Two vaccine doses of pT181‐Qß, without any adjuvants, elicited robust antibody responses in two different mouse models of tauopathy (PS19 and hTau) and rhesus macaques. In mouse models, vaccination reduced AT180+ hyperphosphorylated, Sarkosyl insoluble, Gallyas silver positive tau, inflammasomes/neuroinflammation, and improved recognition memory and motor function without inducing adverse T‐cell activation. Anti‐pT181 antibodies are reactive to pTau in human AD brains, engage pT181+ tau in human brain lysates, and are central nervous system bioavailable. DISCUSSION Our results suggest the translational utility of pT181‐Qß against tauopathies. Highlights Icosahedral display of phosphorylated tau at threonine 181 (pT181) Qß virus‐like particle surface (“pT181‐Qß” vaccine) induces a robust immune response in mice and in non‐human primates (NHPs) pT181‐Qß vaccination reduces pathological tau (pTau) and brain atrophy, and improves memory and motor function in PS19 and hTau mice. pT181‐Qß vaccination–induced immunoglobulin Gs (IgGs) are safe, Th2 skewed (anti‐inflammatory), specific to pTau in human AD brain, and efficiently engage pT181 in NHPs and human brain lysate. pT181+ tau in human plasma correlates with the neurofilament light in subjects with mild cognitive impairment (MCI)—suggesting the presence of pT181‐Qß vaccine target in the early disease state.

INTRODUCTION The “prion‐like” features of Alzheimer's disease (AD) tauopathy and its relationship with amyloid‐β (Aβ) have never been experimentally studied in primates phylogenetically close to humans. METHODS We injected 17 macaques in the entorhinal cortex with nanograms of seeding‐competent tau aggregates purified from AD brains or control extracts from aged‐matched healthy brains, with or without intracerebroventricular co‐injections of oligomeric‐Aβ. RESULTS Pathological tau injection increased cerebrospinal fluid (CSF) p‐tau181 concentration after 18 months. Tau pathology spreads from the entorhinal cortex to the hippocampal trisynaptic loop and the cingulate cortex, resuming the experimental progression of Braak stage I to IV. Many AD‐related molecular networks were impacted by tau seeds injections regardless of Aβ injections in proteomic analyses. However, we found mature neurofibrillary tangles, increased CSF total‐tau concentration, and pre‐ and postsynaptic degeneration only in Aβ co‐injected macaques. DISCUSSION Oligomeric‐Aβ mediates the maturation of tau pathology and its neuronal toxicity in macaques but not its initial spreading. Highlights This study supports the “prion‐like” properties of misfolded tau extracted from AD brains. This study empirically validates the Braak staging in an anthropomorphic brain. This study highlights the role of oligomeric Aβ in driving the maturation and toxicity of tau pathology. This work establishes a novel animal model of early sporadic AD that is closer to the human pathology.

Multimodal neural interfaces that integrate electrical and optical functionalities are promising tools for neuroscientific and clinical applications that involve recording and manipulating neuronal activity. However, most technologies for multimodal implementation are largely restricted to small animal models and lack the ability to translate to the larger brains of non‐human primates (NHPs). Smart Dura, a recently developed large‐scale neural interface for NHPs, enables high‐density electrophysiological recordings and broad optical accessibility, providing multiscale information with enhanced spatiotemporal resolution. In this paper, the multimodal capabilities of Smart Dura are demonstrated through integration with multiphoton imaging, optical coherence tomography angiography (OCTA), and intrinsic signal optical imaging (ISOI), as well as optical manipulations such as photothrombotic lesioning and optogenetics. Through the Smart Dura, in vivo fluorescence vascular imaging is achieved down to depths of 200 and 550 µm using two‐photon and three‐photon microscopy, respectively. When combined with simultaneous electrophysiology, Smart Dura also enables the assessment of vascular and neural dynamics via OCTA and ISOI, the induction of ischemic stroke, and the application of optogenetic neuromodulation across a wide cortical area of 20 mm in diameter. These capabilities support comprehensive investigations of brain dynamics in NHPs, advancing translational neurotechnology for human applications. This study demonstrates multimodal integration in non‐human primates, combining large‐scale, high‐density electrophysiology using Smart Dura with optical techniques such as multiphoton imaging (MPI), photothrombotic lesioning, optical coherence tomography angiography (OCTA), wide‐field intrinsic signal optical imaging (ISOI), and optogenetics. The approach enables simultaneous electrical recording, optical imaging, and neuromodulation across wide cortical areas, providing new opportunities for translational neuroscience and neuroengineering.

With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer's disease (AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non‐human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non‐human primate models of AD was reviewed to provide a theoretical basis for future research.

The sperm epigenome is thought to affect the developmental programming of the resulting embryo, influencing health and disease in later life. Age‐related methylation changes in the sperm of old fathers may mediate the increased risks for reproductive and offspring medical problems. The impact of paternal age on sperm methylation has been extensively studied in humans and, to a lesser extent, in rodents and cattle. Here, we performed a comparative analysis of paternal age effects on protein‐coding genes in the human and marmoset sperm methylomes. The marmoset has gained growing importance as a non‐human primate model of aging and age‐related diseases. Using reduced representation bisulfite sequencing, we identified age‐related differentially methylated transcription start site (ageTSS) regions in 204 marmoset and 27 human genes. The direction of methylation changes was the opposite, increasing with age in marmosets and decreasing in humans. None of the identified ageTSS was differentially methylated in both species. Although the average methylation levels of all TSS regions were highly correlated between marmosets and humans, with the majority of TSS being hypomethylated in sperm, more than 300 protein‐coding genes were endowed with species‐specifically (hypo)methylated TSS. Several genes of the glycosphingolipid (GSL) biosynthesis pathway, which plays a role in embryonic stem cell differentiation and regulation of development, were hypomethylated (<5%) in human and fully methylated (>95%) in marmoset sperm. The expression levels and patterns of defined sets of GSL genes differed considerably between human and marmoset pre‐implantation embryo stages and blastocyst tissues, respectively. Using reduced representation bisulfite sequencing, we identified age‐related differentially methylated transcription start site regions in 204 marmoset and 27 human genes. All identified ageTSS were species‐specific, suggesting flexible evolutionary epigenetic adaptations. Although overall, the TSS methylation levels of orthologous genes were highly correlated in both species, there were also notable between‐species differences, that is, in sperm methylation and postzygotic expression of genes for glycosphingolipid biosynthesis.

Growing evidence indicates that non‐neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP‐43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP‐43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate‐specific cleavage of truncated TDP‐43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP‐43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP‐35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP‐35 in cytoplasm, the downstream myelin‐associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP‐43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP‐43 related diseases. A proposed model of thedemyelination by pathological TDP‐43 in oligodendrocyte. The accumulation of truncated TDP‐43 inoligodendrocyte, could interact with MyRF in the cytoplasm, preventing itsnuclear localization and affecting the expression of myelin‐associated genes, therefore led to the dysfunctional demyelination in corpuscallosum.