Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in AppNL-G-F mice.

Both electroacupuncture (EA) and repetitive transcranial magnetic stimulation (rTMS) possess the potential in combating the progression of Alzheimer's disease (AD). In this study, we compared the effects of the two regimens as early long-term intervention in AppNL-G-F mice, a new amyloid precursor protein (APP) knock-in model that recapitulates multiple AD-associated pathologies, including amyloid-β (Aβ) plaques, microgliosis, astrocytosis, dendritic and synaptic degeneration. The 2-month-old freely moving model mice randomly received EA or rTMS for 2~3 sessions a week for 6 months. Cognitive tests were conducted in Y maze and Barnes maze sequentially at the age of 4, 6, and 8 months. The cortex and hippocampus were dissected thereafter for neurohistological and molecular analysis. Both regimens markedly prevented cognitive deterioration at 6 months old. EA maintained its significant prevention to 8 months old, but rTMS did not. At this age, EA remarkably reduced Aβ burdens with particular dense-core plaques; rTMS had similar effects on Aβ plaques, but not on dense-core plaques. Both regimens displayed greater suppression on microgliosis in the cortex than in the hippocampus, and equivalently inhibited astrocytosis in the two brain regions. While both EA and rTMS protected against dendritic degeneration surrounding Aβ plaques, EA further mitigated synaptic loss. These results demonstrated that EA produced more long-lasting and broad-acting effects than rTMS in alleviating memory impairment and pathological products of AD. EA could serve as an early long-term intervention and rTMS as adjuvant therapy in slowing the progression of AD.