Biology subjects

Nacmias, B.

Publications and source records attributed to Nacmias, B..

2 recordsLinked to original sources

bioRxiv2024

Event-Related Potential Markers of Subject Cognitive Decline and Mild Cognitive Impairment during a sustained visuo-attentive task

Subjective cognitive decline (SCD), mild cognitive impairment (MCI), or severe Alzheimers disease stages are still lacking clear electrophysiological correlates. In 178 individuals (119 SCD, 40 MCI, and 19 healthy subjects (HS)), we analysed event-related potentials recorded during a sustained visual attention task, aiming to distinguish biomarkers associated with clinical conditions and task performance. We observed condition-specific anomalies in event-related potentials (ERPs) during visual encoding (P1/N1/P2) and decision-making (P300/P600/P900): SCD individuals showed attenuated dynamics compared to HS, while MCI individuals showed amplified dynamics, except for P300, which matched clinical severity. ERP features confirmed a non-monotonic trend, with MCI showing higher neural resource recruitment. Moreover, task performance correlated with condition-specific ERP gain and latencies across early and late ERP components. These findings enhanced the understanding of the neural mechanisms underlying cognitive decline in SCD and MCI and suggested potential biomarkers for early diagnosis and intervention. HighlightsO_LIIn encoding (P1/N1/P2) and decision (P600/P900) ERPs, SCD individuals showed attenuated dynamics compared to HS, while MCI individuals exhibited amplified dynamics compared to SCD. C_LIO_LIP300 dynamics matched clinical severity. C_LIO_LIMCI individuals demonstrated higher recruitment of neural resources, indicating a non-monotonic trend in ERP features between clinical conditions. C_LIO_LITask performance correlated with condition-specific gain and latencies across multiple ERP components. C_LI

neuroscience↗

bioRxiv2023

Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction, progression, and prion-like spread of Alzheimer s disease pathogenesis

The hippocampus is a primary region affected in Alzheimers disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis in patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus. Notably, proteomic analysis of the graft enabled the identification of proteomic alterations in AD patient brain cells, associated with increased levels of {beta}-sheet structures and A{beta}42 peptides. Interestingly, the host cells surrounding the AD graft also presented alterations in cellular biological pathways. Furthermore, proteomic analysis across human iPSC-based models and human post-mortem hippocampal tissue projected coherent longitudinal cellular changes indicative of disease progression from early to end stage AD. Our data showcase patient-based models to study the cellular origin, progression, and prion-like spread of AD pathogenesis. Highlights- AD patient iPSC-derived brain cells survive in the hippocampus of immunodeficient mice 6 months post-transplantation. - Proteomic analysis of the grafts reveals profound alterations in cellular biological pathways in iPSC-derived hippocampal cells despite absence of senile plaques. - Proteomic alterations within transplanted AD iPSC-derived hippocampal cells are reminiscent of early/prodromal AD. - AD-grafted cells induce proteomic changes in host mouse cells.

neuroscience↗