Ginkgo biloba L. extract reverses memory impairment in older female mice with cholinergic dysfunction

Aging-induced neurochemical changes in the dentate gyrus (DG) impair memory, a process accelerated in late-onset Alzheimer's disease (LOAD). LOAD is characterized by neuronal loss, amyloid-β (Aβ) plaques, tau tangles, and reduced cholinergic signaling. Current pharmacological therapies for AD offer only symptomatic relief and fail to halt or reverse disease progression. Given previous findings of cognitive benefits and neuroprotection, standardized Ginkgo biloba L. leaf extract (EGb) is being explored as a promising multi-target strategy to address these complex neuropathological features and reverse memory impairments.

Researchers evaluated chronic EGb treatment in older female wild-type mice and two lines of VAChT knockdown mice (KDHET and KDHOM), which exhibit 45% and 65% reductions in VAChT expression, respectively. The study assessed the impact of EGb on memory, anxiety-like behaviors, and motor activity. Additionally, the researchers quantified Aβ1-42 peptide and phosphorylated tau (pTauT231) by counting Aβ IR+ and pTau IR+ cells in the dCA1, dCA3, and dDG regions using immunohistochemistry. An in vitro component also investigated EGb's effect on Aβ aggregation.

Aging significantly led to short- and long-term memory deficits, which were notably exacerbated in the VAChT KDHOM mice. However, chronic EGb treatment effectively reversed these memory deficits in a dose-dependent manner. This reversal was associated with EGb's ability to modulate Aβ and pTau-IR+ cells within the dCA1 and dDG regions of the hippocampus.

EGb treatment reversed memory deficits in VAChT KDHOM mice, which showed 65% reduced VAChT expression, by modulating Aβ and pTau-IR+ cells. Furthermore, in vitro experiments demonstrated that EGb significantly inhibited Aβ aggregation through direct interactions with Aβ and the POPC monolayer. These findings collectively suggest that EGb targets key neuropathological features of AD, offering both cognitive improvement and neuroprotection.