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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Neurobiol Aging. 2022 Mar 22;115:20–28. doi: 10.1016/j.neurobiolaging.2022.03.011

Fig. 2.

Fig. 2.

Therapeutic approaches of apoE4 reduction for AD therapies. ApoE4 reduction leads to attenuation of neuroinflammation and alleviation of amyloid and tau pathologies in the AD brain. Specific apoE ASOs and siRNAs are promising therapeutic approaches to directly reduce apoE levels for the treatment of AD patients carrying APOE ε4 allele. In addition, the IDOL/PCSK9-LDLR-apoE axis provides an alternative approach to indirectly reduce apoE4 levels for AD therapies. Specific IDOL ASOs, and PCSK9 inhibitors Pep2–8 and Alirocumab (Aliro) display significant therapeutic effects on alleviation of pathological changes in experimental AD models.