The APOE4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD), while APOE2 is protective and APOE3 is neutral. However, APOE4-related risk is not uniform: Latinos exhibit different genetic risk patterns compared to non-Latinos despite higher overall AD prevalence, underscoring the need to understand these disparities. Memory—one of the earliest cognitive functions affected in AD—relies on hippocampal function. Although APOE4 has been linked to poorer memory, its role in emotional memory remains underexplored. This study examines emotional memory performance across APOE genotypes to identify cognitive and emotional differences and assess the influence of age and ethnicity. Latino and non-Latino participants (ages 18–89; N=376) completed an emotional memory task, with a subset (N=142) undergoing high-resolution fMRI to measure hippocampal and amygdala activity—regions critical for emotional memory and affected early in AD. Participants were grouped by genotype: high risk (E3/E4, E4/E4), neutral (E3/E3), and low risk (E2/E3, E2/E2). Results showed that genetic risk effects varied by memory type: interactions between genetic risk and ethnicity influenced general memory, while only genetic risk affected detailed memory. fMRI findings revealed that lower-risk individuals showed reduced hippocampal hyperactivity during accurate memory. Overall, these findings clarify how APOE4 influences emotional memory and may inform early detection and intervention strategies.

Magnetically aligned nanoparticle fibers are capable of forming anisotropic scaffolds that may guide cellular organization at spinal cord injury sites. Previous studies demonstrated that these fibers form rapidly and remain stable under cell-free conditions, but lose continuity in astrocyte cultures due to clustering and intracellular uptake. The present study investigates whether introducing a defined cell-cell adhesion mechanism can stabilize these structures. The primary objective is to determine whether N-cadherin functionalization shifts astrocyte interactions from disruptive remodeling to stable attachment along aligned fibers. Streptavidin-coated magnetic nanoparticles are functionalized with a Ni-Tris-NTA-biotin system to present His-tagged N-cadherin at controlled surface densities. Aligned fibers are generated under standardized magnetic field conditions and applied to human astrocyte cultures. Interactions are evaluated at acute and multi-day timepoints using microscopy-based quantification of fiber continuity, clustering, and retention after wash steps to distinguish extracellular alignment from intracellular accumulation. This study evaluates whether cadherin-mediated adhesion preserves aligned fiber architecture in astrocyte-rich environments. Establishing stable and continuous cellular substrates would address a key limitation in scaffold-based strategies designed to support axonal growth across spinal cord injury lesions.

Associative learning is essential for predicting meaningful outcomes. One form, higher-order conditioning, occurs when a neutral cue gains meaning through its association with another learned cue. For example, a restaurant sign (cue 1) may be associated with food (reward), while a nearby landmark such as a statue (cue 2) predicts the restaurant sign. Over time, the landmark can also gain meaning through this indirect relationship. In this pilot study, we tested whether a second cue can acquire significance through its relationship with a first cue and become linked to the reward. In Experiment A, rats were familiarized with cues, then trained to associate one auditory cue with a reward, followed by pairing a second auditory cue with the first. Test sessions assessed responding to both cues. Second-order responding did not reliably emerge, and animals also responded to unpaired cues, similar to reacting to unrelated landmarks in the example. Experiment B strengthened control conditions and introduced outcome devaluation using a malaise-inducing agent, similar to developing food poisoning after eating at the restaurant. Under these conditions, paired rats showed increased responding to the second cue, which decreased after devaluation, indicating that their response depended on the expected reward. These findings suggest the refined procedure better captures higher-order associative processes and provides a foundation for future studies incorporating neural recording and optogenetic approaches.

PLCG2 mediates key signaling pathways to regulate immune and inflammatory responses. Studies link a rare allele of PLCG2 (rs72824905-G, resulting in a missense P522R mutation) to increased longevity (OR = 1.49 for reaching age 90). Notably, this variant is a prominent Alzheimer’s disease-protective allele (OR = 0.57-0.68) and lowers risk for other forms of dementia, suggesting that PLCG2 may play a pivotal role in aging and neurodegenerative diseases. To investigate PLCG2 involvement in longevity, we performed immunohistochemical analyses on brain sections from wild-type and Plcg2-P522R knock-in mice at 4 and 24 months old. While microglia numbers and Iba1 levels remained unchanged, Plcg2-P522R significantly reduced the expression of GFAP, an astrocyte marker, suggesting an attenuation of neuroinflammation in Plcg2-P522R mice. We also assessed synaptic and neuronal markers (vGlut1, vGlut2, synaptophysin, PSD95, and NeuN), revealing age- and genotype-dependent changes in synaptic integrity. To assess functional outcomes, we performed the novel object recognition test. We found that old Plcg2-P522R mice demonstrated better episodic memory than age-matched old wildtype mice. These findings suggest that PLCG2-P522R may lower neuroinflammation to promote synaptic integrity and subsequently preserve cognitive function during aging. While further analyses of neuroinflammatory signaling are needed, this variant represents a potential therapeutic target for enhancing healthy brain aging and mitigating age-related cognitive decline.