The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021-2025 State-of-the-Art Review of Clinical and Preclinical Evidence.

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.