While the classical pathway in the liver is responsible for most BA synthesis, the brain uses the alternative and neural pathways to clear cholesterol, leading to the production of BAs . The intermediates of the alternative pathway are explained in S2.2 and Figure . The primary BAs, cholic acid (CA) and chenodeoxycholic acid (CDCA) presented a non-significant higher trend in MCI and AD compared to the ND group (Figure ). In contrast, the glycine conjugated primary BAs glycocholic acid (GCA) and glycochenodeoxycholic acid (GCDCA), top right of Figure , showed significantly lower concentrations in the AD compared to the MCI group. Elevated concentrations of these two BAs were previously reported in AD plasma samples compared with control subjects . Therefore, CSF concentrations may not always reflect circulating BAs levels.