Sex and life experience shape locus coeruleus pretangle tau pathology - PubMed
14 hours ago
- #Alzheimer's disease
- #locus coeruleus
- #tau pathology
- Alzheimer's disease involves early pathology in the locus coeruleus (LC), with sex and life experience influencing its vulnerability.
- Study used TH-Cre rats expressing pseudophosphorylated human tau (htauE14) in LC neurons, exposing sexes to early/late-life enrichment or stress.
- htauE14 in LC impaired learning and increased anxiety-like behavior.
- Early enrichment reduced htauE14 spread and LC microglia activation, increased hippocampal BDNF, and improved olfactory learning in males.
- Late enrichment alleviated anxiety and enhanced spatial memory, while late stress worsened LC degeneration.
- Hippocampal snRNA-seq showed sex- and cell type-specific responses, with htauE14 affecting metabolic and synaptic pathways more in females.
- Early stress amplified htauE14 effects in females, while early enrichment stabilized them.
- Late-life experiences mainly influenced homeostatic regulatory programs.
- Sex and developmental history critically affect early LC tau-related vulnerability.