Biology subjects

Badawy, M.

Publications and source records attributed to Badawy, M..

3 recordsLinked to original sources

bioRxiv2026

CSF complement proteins are associated with early tau pathology and synaptic damage in an asymptomatic population at risk of Alzheimer's disease

Complement-mediated neuroinflammation has been implicated in Alzheimer's disease (AD), but its role during the pre-symptomatic phase of the disease remains unclear. In the PREVENT-AD cohort of cognitively unimpaired individuals at increased familial risk of AD, we investigated whether CSF complement proteins relate to early AD pathology and synaptic dysfunction, then assessed our results' reproducibility across the clinical AD spectrum. Baseline CSF C1q, C3, C3b, and Factor H were measured in relation to CSF AD biomarkers, synaptic proteins, cognition, MRI volumetry, and amyloid and tau PET. Key findings were then examined in 708 participants from ADNI spanning cognitively normal, mild cognitive impairment (MCI), and dementia stages of AD. In PREVENT-AD, C1q was positively associated with CSF P-tau181, T-tau, and multiple synaptic markers including ADAM23, GAP43, SNAP25, and SYT1. Factor H showed similarly strong positive associations with P-tau181, T-tau, ADAM22, ADAM23, GAP43, and SYT1. By contrast, C3 showed minimal associations, while C3b displayed weaker positive relationships with P-tau181, T-tau, ADAM22, and ADAM23. Complement proteins were not robustly associated with amyloid or tau PET, and only C1q related to lower global cognitive performance. In ADNI, C1q emerged as the most consistent analyte, showing positive associations with tau, neurofilament light, and synaptic markers across all diagnostic groups. C3 exhibited predominantly negative associations, whereas C3b and Factor H showed stage-dependent relationships, particularly with evident neurodegeneration and synaptic injury in symptomatic individuals. These findings identify complement dysregulation, especially involving C1q, as an early correlate of tau-linked synaptic pathology, and support a role for complement activation in the AD molecular cascade.

neuroscience↗

bioRxiv2026

A UNIFORM CODING STRUCTURE IN THE CEREBRAL CORTEX

Prefrontal neurons simultaneously encode multiple task variables. While many studies reported that various groupings of task features could be detected at the population level, the combination of features encoded by individual neurons seemed random. Here, based on unit recordings with Neuropixel probes in behaving rats, we report that far from being random, the representation of information is highly structured. Specifically, the prefrontal network exhibits multiple coding gradients orthogonal to each other in a multidimensional representational space. In this coding structure, neurons have correlated absolute firing rate modulations by different variables, but the polarity of the modulation by one variable is not predictive of that by others. Moreover, this coding structure is manifest in tasks that probe different behavioral processes, ranging from defensive behaviors to sensory discrimination. Last, we find that the same structured representation is apparent in other neocortical regions, including associative and primary sensory areas.

neuroscience↗

bioRxiv2025

Screening channelrhodopsins using robotic intracellularelectrophysiology and single cell sequencing

BackgroundOur ability to engineer opsins is limited by an incomplete understanding of how sequence variations influence function. The vastness of opsin sequence space makes systematic exploration difficult. New methodIn recognition of the need for datasets linking opsin genetic sequence to function, we pursued a novel method for screening channel-rhodopsins to obtain these datasets. In this method, we integrate advances in robotic intracellular electrophysiology (Patch) to measure optogenetic properties (Excite), harvest individual cells of interest (Pick) and subsequently sequence them (Sequence), thus tying sequence to function. ResultsWe used this method to sequence more than 50 cells with associated functional characterization. We further demonstrate the utility of this method with experiments on heterogeneous populations of known opsins and single point mutations of a known opsin. Of these point mutations, we found C160W ablates ChrimsonRs response to light. Conclusion and comparison to existing methodsCompared to traditional manual patch clamp screening, which is labor-intensive and low-throughput, this approach enables more efficient, standardized, and scalable characterization of large opsin libraries. This method can enable opsin engineering with large datasets to increase our understanding of opsin sequence-function relationships.

neuroscience↗