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Alternative splicing in Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder in the elderly, occurring in approximately 20% of people older than 80. The molecular causes of AD are still poorly understood. However, recent studies have shown that Alternative Splicing (AS) is involved in the gene expression reprogramming associated with the functional changes observed in AD patients. In particular, mutations in cis-acting regulatory sequences as well as alterations in the activity and sub-cellular localization of trans-acting splicing factors and components of the spliceosome machinery are associated with splicing abnormalities in AD tissues, which may influence the onset and progression of the disease. In this review, we discuss the current molecular understanding of how alterations in the AS process contribute to AD pathogenesis. Finally, recent therapeutic approaches targeting aberrant AS regulation in AD are also reviewed.

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Acknowledgements

We apologize to the authors of many interesting and important papers that have not been cited in this review.

Funding

This work was supported by the National Research Council of Italy (CNR), Research Project “Aging: molecular and technological innovations for improving the health of the elderly population” (Prot. MIUR 2867 25.11.2011) and AMANDA project Accordo Quadro Regione Lombardia–CNR to G.B. E.B. is supported by AIRC - FIRC ITALY postdoctoral fellowship; D.P. is awarded with a Arturo Falaschi - Fondazione Adriano Buzzati-Traverso (FAB-T) postdoctoral fellowship.

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  1. Angela Amato, Elisa Belloni, Anna Di Matteo, Lucia Infantino and Davide Pradella contributed equally to this work.

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  1. Istituto di Genetica Molecolare “Luigi Luca Cavalli-Sforza”, Consiglio Nazionale delle Ricerche (IGM-CNR), via Abbiategrasso, 207, 27100, Pavia, Italy

    Giuseppe Biamonti, Angela Amato, Elisa Belloni, Anna Di Matteo, Lucia Infantino, Davide Pradella & Claudia Ghigna

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  1. Giuseppe Biamonti
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All authors contributed to all parts of the present review including papers selection, information synthesis, and paper drafting/editing. All authors approved and verified the final version.

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Correspondence to Giuseppe Biamonti.

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C.G. is a consultant for Gene Tools. Funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Biamonti, G., Amato, A., Belloni, E. et al. Alternative splicing in Alzheimer’s disease. Aging Clin Exp Res 33, 747–758 (2021). https://doi.org/10.1007/s40520-019-01360-x

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