The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021–2025 State‐of‐the‐Art Review of Clinical and Preclinical Evidence
6 affiliations
- 1Independent Researcher Messina Italy
- 2Departmental Faculty of Medicine UniCamillus‐Saint Camillus International University of Health Sciences Rome Italy
- 3IRCCS San Camillo Hospital Venice Italy
- 4Department of Biomedical and Biotechnological Sciences University of Catania Catania Italy
- 5IRCCS Centro Neurolesi Bonino‐Pulejo Messina Italy
- 6Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina Messina Italy
Abstract
Statins, widely prescribed for cardiovascular prevention, have emerged as potential disease-modifying agents in neurodegenerative disorders due to their pleiotropic effects on cholesterol metabolism, neuroinflammation, oxidative stress, and protein aggregation. Over the past decade, growing interest has focused on the potential repurposing of statins for Parkinson's disease (PD) and Alzheimer's disease (AD); however, clinical evidence remains heterogeneous and, in some cases, contradictory. This state-of-the-art review synthesizes clinical and preclinical studies published between 2021 and 2025 to critically evaluate the therapeutic potential and limitations of statins in PD and AD. Recent observational studies and large-scale cohort analyses suggest that long-term statin use may be associated with a reduced risk of incident PD and AD, as well as slower cognitive decline in selected patients' subgroups. However, these associations appear to depend on factors such as statin lipophilicity, treatment duration, and genetic background. Preclinical models provide mechanistic support, showing that statins can attenuate neuroinflammation, modulate microglial activation, reduce α-synuclein aggregation in PD models, and interfere with amyloid-β production and tau phosphorylation in AD models. Nevertheless, randomized controlled trials remain limited in number and often underpowered, and some reports indicate neutral or even adverse neurological outcomes, underscoring the complexity of cholesterol-dependent and cholesterol-independent mechanisms in the central nervous system (CNS). Collectively, the evidence from 2021 to 2025 highlights both the therapeutic promise and the unresolved challenges of statin repurposing in neurodegenerative diseases. Future research should prioritize well-designed clinical trials and biomarker-driven patient stratification to determine whether statins can be effectively leveraged as adjunctive disease-modifying therapies in PD and AD.
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BibTeX
@article{chiatto2026statins,
title = {{The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021–2025 State‐of‐the‐Art Review of Clinical and Preclinical Evidence}},
author = {Luigi Maria Chiatto and Lucia Buccarello and Giuseppe Carota and Rocco Salvatore Calabrò and Carmela Rifici and Emanuela Esposito and Alessio Ardizzone and Giuseppe Caruso},
journal = {Pharmacology Research \& Perspectives},
year = {2026},
month = jun,
doi = {10.1002/prp2.70280},
url = {https://doi.org/10.1002/prp2.70280},
note = {CC BY},
}
RIS
TY - JOUR
TI - The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021–2025 State‐of‐the‐Art Review of Clinical and Preclinical Evidence
AU - Luigi Maria Chiatto
AU - Lucia Buccarello
AU - Giuseppe Carota
AU - Rocco Salvatore Calabrò
AU - Carmela Rifici
AU - Emanuela Esposito
AU - Alessio Ardizzone
AU - Giuseppe Caruso
PY - 2026
DA - 2026/06/01
JO - Pharmacology Research & Perspectives
DO - 10.1002/prp2.70280
UR - https://doi.org/10.1002/prp2.70280
AB - Statins, widely prescribed for cardiovascular prevention, have emerged as potential disease-modifying agents in neurodegenerative disorders due to their pleiotropic effects on cholesterol metabolism, neuroinflammation, oxidative stress, and protein aggregation. Over the past decade, growing interest has focused on the potential repurposing of statins for Parkinson's disease (PD) and Alzheimer's disease (AD); however, clinical evidence remains heterogeneous and, in some cases, contradictory. This state-of-the-art review synthesizes clinical and preclinical studies published between 2021 and 2025 to critically evaluate the therapeutic potential and limitations of statins in PD and AD. Recent observational studies and large-scale cohort analyses suggest that long-term statin use may be associated with a reduced risk of incident PD and AD, as well as slower cognitive decline in selected patients' subgroups. However, these associations appear to depend on factors such as statin lipophilicity, treatment duration, and genetic background. Preclinical models provide mechanistic support, showing that statins can attenuate neuroinflammation, modulate microglial activation, reduce α-synuclein aggregation in PD models, and interfere with amyloid-β production and tau phosphorylation in AD models. Nevertheless, randomized controlled trials remain limited in number and often underpowered, and some reports indicate neutral or even adverse neurological outcomes, underscoring the complexity of cholesterol-dependent and cholesterol-independent mechanisms in the central nervous system (CNS). Collectively, the evidence from 2021 to 2025 highlights both the therapeutic promise and the unresolved challenges of statin repurposing in neurodegenerative diseases. Future research should prioritize well-designed clinical trials and biomarker-driven patient stratification to determine whether statins can be effectively leveraged as adjunctive disease-modifying therapies in PD and AD.
SN - 2052-1707
ER -