Concerning the ApoE4 variant, regardless of AD diagnosis, older adults that are ApoE4 + display a greater level of A accumulation that is not evident in ApoE3 + or ApoE2 + individuals (Lim et al., 2017), and AD patients with the ApoE4 genotype ( +/+ or +/ ) display higher levels of intraneuronal A accumulation compared to controls, indicating a baseline detrimental cognitive effect (Yamazaki et al., 2019)
Further support was provided by the Uehara Memorial Foundation, Kanae Foundation for the Promotion of Medical Science, Mochida Memorial Foundation for Medical and Pharmaceutical Research and the Human Frontier Science Program, plus the Medical Scientist Training Program and Pharmacology Training Grant at UC San Diego (T32GM007752)
The unfortunate truth is that big risk signals (lets say the kind you get from drinking antifreeze) can be spotted from the anecdotal experience of people in the world just trying things, but small-but-serious risk signals (lets say cardiovascular disease with tofacitinib) are really hard to identify without a proper trial or a proper observational study
Redox Signal 20 (4), 545556
demonstrated the oral bioavailability and safety of NR in humans (Trammell et al