Common drug combinations affect Alzheimer's Disease pathology differently in male and female mice

Certain widely used drug combinations may either slow down or worsen the progression of Alzheimer's disease, but their effects differ between sexes. A new study from Karolinska Institutet, published in Alzheimer's & Dementia , highlights these important findings. Millions of older adults take multiple medications daily to manage conditions such as high blood pressure , high cholesterol, and depression—diseases that are also linked to Alzheimer's.

But how do these commonly prescribed drugs, when taken together, influence the course of Alzheimer's disease? Researchers have investigated this question by studying two widely used drug combinations in Sweden in male and female mice with Alzheimer's-like brain changes. The researchers tested a five-drug combination consisting of a beta-blocker, a statin, an antidepressant, an anticoagulant, and a pain reliever. Their results showed that this combination improved memory and reduced Alzheimer's-related brain changes in male mice, whereas female mice showed little to no benefit.



However, when the researchers replaced two of the cardiovascular drugs with alternative medications, the benefits for males were lost, and female mice experienced worsening memory. "Our findings emphasize the importance of considering sex differences when evaluating the effects of medications in Alzheimer's disease," say Silvia Maioli, Associate Professor and Principal Researcher, and Francesca Eroli, Ph.D.

student at the Department of Neurobiology, Care Sciences and Society at Karolinska Institutet. Toward more personalized treatments In addition to assessing memory function, the researchers analyzed the brains and blood of the mice. They identified biological markers that could help predict how different individuals respond to specific drug combinations.

"The next step is to investigate why these differences occur and to identify biomarkers that could help us predict which patients will benefit from certain treatments. In the long term, this could pave the way for more personalized medication strategies," says Maioli. More information: Francesca Eroli et al, Commonly prescribed multi-medication therapies exert sex-specific effects on Alzheimer's disease pathology and metabolomic profiles in App NL-G-F mice: Implications for personalized therapeutics in aging, Alzheimer's & Dementia (2025).

DOI: 10.1002/alz.70081 .

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