Sex-Specific Catecholaminergic Dysfunction Underlie Proactive Interference deficits in APPswe/PS1dE9 Mice
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Interference is a major contributor to early memory decline in Alzheimer’s disease (AD). We investigated whether proactive interference (PI) destabilizes recognition memory in 2-month-old APP/PS1 mice, a stage when novel object recognition (NOR) is normally intact. PI selectively impaired recognition in male, but not female, APP/PS1 mice, revealing a sex-specific vulnerability. At the neuromodulatory level, male APP/PS1 mice displayed reduced tyrosine hydroxylase–positive dopaminergic terminals in dorsal not ventral hippocampal subfields, whereas females were spared. These results identify PI as a sensitive probe of early recognition instability in AD and highlight sex-divergent mechanisms in which males not females show catecholaminergic vulnerability.
