Gut microbial metabolite found in fruits like pomegranates and berries, significantly improved cognitive functions in mouse models of Alzheimer's disease, according to a recent study.

Researchers administered long-term urolithin A (UA) treatment to three different Alzheimer's disease (AD) mouse models: APP/PS1, 3xTgAD, and 3xTgAD/Polβ+/− mice. The treatment lasted for 5 months, and its effects were assessed through behavioral, electrophysiological, biochemical, and bioinformatic analyses. The study found that UA significantly improved learning, memory, and olfactory functions in the treated mice. In the Morris water maze test, UA-treated mice took less time to reach the hidden platform compared to untreated mice. These beneficial effects persisted for 1 month after UA was discontinued in the APP/PS1 mice.

UA reduced amyloid beta (Aβ) and tau pathologies and improved long-term potentiation in the brain. The effects appeared to be mediated through the restoration of mitophagy and lysosomal functions. UA restored lysosomal activity and normalized cathepsin Z (Ctsz) levels, indicating that cathepsins may play a role in UA-induced effects on AD. Additionally, UA modulated immune responses and AD-specific pathways, reducing neuroinflammation markers such as IL-1β and NF-κB.

The study, published in Alzheimer's & Dementia, showed that UA increased the expression of mitophagy-related proteins, such as Parkin and BNIP3, and decreased DNA damage markers like γ-H2AX in the AD mouse brains. The results were largely consistent across the three AD mouse models, supporting the evidence for UA's potential. The researchers concluded that the evidence supports UA as a potential agent targeting AD-related neurodegeneration.

Full list of disclosures is available in the original study.