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Leger, M.

Publications and source records attributed to Leger, M..

2 recordsLinked to original sources
bioRxiv2026

Proteomic signatures of cognitive resilience in LOU/c/Jall rats converge with inverse hippocampal axes of Alzheimer disease.

Why some individuals maintain good level of cognitive performances during aging, others dont or even progress toward Alzheimers disease. We profiled the hippocampal proteome of adult LOU/c/Jall rats, a strain associated with spontaneous cognitive longevity, and compared this proteomic state with a published human hippocampal Alzheimers disease dataset. Because individual protein changes did not survive proteome-wide correction, interpretation was based on convergent pathway-level, cell-type enrichment and cross-species directional analyses. The LOU hippocampus displayed a structured remodeling of mitochondrial, lysosomal, proteostatic and synaptic systems. Oligodendrocyte-associated nuclear-encoded complex I/III components were reduced, whereas neuronal mitochondrial aminoacyl-tRNA synthetases, V-ATPase, SNARE-related proteins and inhibitory-transmission markers were increased. CD200 was markedly reduced, but this occurred without accompanying complement, microglial, astrocytic or inflammatory activation signatures. Cross-species overlay indicated that several LOU-associated axes were directionally opposed to late Alzheimers disease, particularly synaptic vesicle and inhibitory-transmission programs, whereas myelin-associated changes occupied a lower-amplitude and non-inflammatory position along an axis altered in early Alzheimers disease. These findings identify a hippocampal proteomic configuration associated with the LOU resilience phenotype and suggest that successful brain aging and Alzheimers disease may involve opposing states of shared hippocampal molecular systems. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/735140v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@8a1a17org.highwire.dtl.DTLVardef@b7023corg.highwire.dtl.DTLVardef@f3ca20org.highwire.dtl.DTLVardef@15b1b29_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIHippocampal proteome of the LOU/c/Jall rat at 3 months profiled by DIA-MS C_LIO_LICoordinated reduction of complex I/III subunits in oligodendrocytes C_LIO_LINeuronal aminoacyl-tRNA synthetases, V-ATPase and SNARE machinery up-regulated C_LIO_LIMarked reduction of CD200 with no inflammatory correlate C_LIO_LILate human AD hippocampal transcriptome moves opposite to adult LOU C_LI

neuroscience↗
bioRxiv2026

DIVERGENT TRAJECTORIES FOR ANAEROBIC MITOCHONDRIAL EVOLUTION IN BREVIATE PROTISTS

Mitochondrion-related organelles (MROs) have evolved as adaptations to low oxygen conditions multiple times in the eukaryote tree of life. However, the evolutionary steps by which aerobic mitochondrial functions were replaced by anaerobic pathways are still poorly understood. The breviate Pygsuia biforma is particularly interesting because it is the only protist known to have replaced the canonical mitochondrial iron-sulfur cluster (ISC) system with a horizontally acquired SUF-like minimal system (SMS) protein. This functions within an MRO possessing a uniquely configured electron transport chain (ETC). To investigate the evolutionary path by which the P. biforma MRO evolved these features, we conducted a comparative transcriptomic study of eight diverse marine breviate species and predicted their MRO proteomes. We found three distinct patterns of iron-sulfur cluster biosynthesis machinery across the breviates where organisms would encode: the canonical ISC system alone, the ISC system and cytoplasmic SMS system, and a cytoplasmic and MRO-localized SMS system. Phylogenetic analyses suggests that the SMS system was acquired via lateral gene transfer in an ancestor of all breviates and later duplicated, with one copy gaining mitochondrial targeting and replacing the ISC system in a subset of breviates. We observed similarly divergent evolutionary trajectories for quinone-utilizing proteins. Two species have completely lost the ETC while the remaining lineages retain a partial ETC and mitochondrial contact site and cristae organizing system (MICOS), previously thought to be absent in breviates. These patterns reflect divergent biochemical configurations of MROs shaped by gene transfer, loss, and duplication within a single eukaryotic lineage and underscores dynamic remodeling of organellar metabolism in response to marine hypoxic environments.

evolutionary biology↗