Table 4.

Major non-anti-amyloid AD treatments under investigation.

Reference	Drug target	Mechanism	Brief conclusions
Fitz et al. (2019)	Retinoid X Receptors	Important for APOE expression, retinoid acid-mediated signaling, neuronal plasticity, and memory; anti-inflammatory effects of RXR/LXR.	Research is focused on activating LXR/RXR in the brain using nonsteroid synthetic ligands. Mice studies have seen variable outcomes.
Fitz et al. (2019)	Liver X Receptors	Include LRXα and LRXβ. LRXs are transcriptional regulators of lipid metabolism and inflammation. LRXβ is expressed in brain and spinal cord as the brain is the most cholesterol-rich organ and peripheral cholesterol cannot cross BBB. LRXβ K/O mice display motor neuron degeneration and impaired coordination.	Early phases of research; still needs validation in animal studies but has shown reduced levels of insoluble Aβ in mice. Research is focused on activating LXR/RXR in the brain using nonsteroid synthetic ligands.
Fitz et al. (2019)	Nuclear Receptors	Widely expressed in the brain. By directly binding to PPARs and LXRs, nuclear receptors ultimately induce stabilization of nuclear complexes that promote neuro- and peripheral inflammatory genes.	Early phases of research; still needs validation in animal studies.

Abbreviations: RXR, retinoid X receptors; APOE, apolipoprotein E; LXR, liver X receptors; BBB, blood-brain-barrier; K/O, knock-out; PPAR, peroxisome proliferator-activated receptor.