Alzheimer’s Disease Risk Factors & Sex-Specific Mechanisms – Silvia Maioli's research group

Alzheimer’s disease (AD) results from a complex interaction of genetic, environmental, and age-related factors. Our research focuses on the interplay between biological sex (female vs. male) and cholesterol-related environmental and genetic risk factors (hypercholesterolemia, APOE4 genotype), using mouse models and human clinical and postmortem samples. By identifying sex-specific pathways that drive disease progression, we aim to develop tailored strategies for AD prevention and treatment.

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Latest news from our research group

Our research

🧬  Cholesterol, Brain Health & Alzheimer’s
Alterations in brain cholesterol metabolism are central to neurodegenerative processes. We explore how the APOE4 genotype, brain cholesterol turnover, and cholesterol-derived metabolites (such as oxysterols) influence cognitive function and AD progression.

🧠  Sex Differences in Alzheimer’s Risk
Women are at a higher risk for Alzheimer's disease (AD), partially due to hormonal changes, among other factors, that affect brain metabolism. Our research investigates how sex hormones, cholesterol metabolism, and genetic factors contribute to sex-specific disease pathways and influence treatment responses.

🔬  CYP46A1 as a Therapeutic Target for women at risk 
Our research has shown that overexpressing CYP46A1 improves memory in aging and estrogen deprived female mice. We explore pharmacological and genetic strategies to increase CYP46A1 activity as a potential neuroprotective therapy for women at higher risk of AD.

🔍  Early Biomarkers for Women at Risk
We analyze biomarkers in blood and cerebrospinal fluid, such as cholesterol metabolites, to identify high-risk women and improve early detection strategies for AD.

💊  Multi-Drug Therapies & Sex-Specific Effects
Many older adults, including AD patients, take multiple medications (polypharmacy), but their effects differ by sex. We investigate how commonly prescribed drug combinations impact cognition, metabolism, and AD progression using preclinical models and human cohort data to guide personalized treatment strategies .

Publications

All publications from group members

Staff and contact

Group leader

  • Silvia Maioli
    Principal Researcher | Docent

    Principal Researcher studying sex-specific mechanisms in Alzheimer’s disease, focusing on cholesterol metabolism, translational approaches, and women’s health.

All members of the group

Visiting address

Karolinska Institutet, Neurobiology Care Sciences and Society, Bioclinicum, Solnavägen 30, Stockholm, Sweden

Patricia Rodriguez research

Team members

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Patricia Rodriguez Rodriguez

Team leader
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Christina Tsagkogianni

Phd Student

Beatrice Mattina

Affiliated to Research

Research focus

 

Our research is focused on understanding how different genetic and non-genetic risk factors and disease drivers trigger the early degeneration of specific regions and neuronal subpopulations in Alzheimer's disease. To achieve this goal we apply a wide variety of cell-type specific transcriptomics and proteomics approaches in human post-mortem brain samples, mouse models and in-vitro systems.

Projects

 

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   Rodriguez-Rodriguez P et al.  bioRxiv, 2025:
   https://pubmed.ncbi.nlm.nih.gov/39803521/

 

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   Rodriguez-Rodriguez P et al.  Brain, 2024: 
   https://pubmed.ncbi.nlm.nih.gov/38462574/

Collaborations

 

Dr. Jean-Pierre Roussarie. Boston University Chobanian & Avedisian school of medicine (Boston, USA). https://www.bumc.bu.edu/anatneuro/roussarie-lab/

Identification of tau pathology drivers in Alzheimer’s disease vulnerable neurons.

Roussarie JP et al. Neuron, 2020:https://pubmed.ncbi.nlm.nih.gov/32603655/

 

Dr. Joana Braga Pereira. Karolinska Institute (Sweden). https://ki.se/en/research/research-areas-centres-and-networks/research-groups/brain-connectomics-pereiras-lab-joana-pereiras-research-group

Region-specific neuroimaging-based genome-wide association study to identify novel risk and resilience factors for Alzheimer’s disease.

 

Dr. Ana Milosevic. The Rockefeller University (NYC, USA). https://shahamlab.rockefeller.edu/research.php

Region-specificity of astrocytes and their contribution to Alzheimer’s disease and major depressive disorder.

Zhang et al. bioRxiv, 2024. https://pubmed.ncbi.nlm.nih.gov/39803419/

Zhang et al. bioRxiv, 2022. https://doi.org/10.1101/2022.11.16.515390

 

Funding

Alzheimerfonden: https://www.alzheimerfonden.se/nyheter/alzheimerfonden-samlade-in-81-miljoner-kronor-under-2024/

KID-funding: https://staff.ki.se/doctoral-education/internal-ki-funding-for-doctoral-education/kid-funding

Private initiative “Innovative ways to fight Alzheimer’s disease- Leif Lundblad Family and others”

Petrus och Augusta Hedlunds Stiftelse: http://www.hedlundsstiftelse.se

Konung Gustaf V:S och drottning Victoria Stiftelse: https://frimurarorden.se/konung-gustav-vs-och-drottning-victorias-frimurarestiftelse/

European commission MSCA actions: https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/projects-details/31045243/799638/H2020

Stiftelsen för Gamla Tjänarinnor: https://www.stiftelseansokan.se/Pages/GamlaTjanarinnor.aspx

Gun och Bertil Stohnes Stiftelse: https://www.stohnesstiftelse.se/sv-SE