. Protective Alzheimer's disease-associated APP A673T variant predominantly decreases sAPPβ levels in cerebrospinal fluid and 2D/3D cell culture models. Neurobiol Dis. 2023 Jun 15;182:106140. Epub 2023 Apr 28 PubMed.


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  1. This study reports a very important finding for Alzheimer's disease and specifically for the development of BACE1-targeted inhibitors. The study demonstrates that the protective Icelandic mutation—located close to the BACE1 cleavage site in APP—lowers CSF Aβ42 by nearly 30 percent. A similar reduction was previously reported by the same group, but in plasma. Importantly, this mild CSF Aβ42 reduction—which, however, occurs life-long—correlated with the absence of amyloid and tau pathology. This new data suggests that a mild inhibition of BACE1 (less than 50 percent) may be a reasonable strategy for prevention of Alzheimer's disease. Further considerations on low-level BACE1 inhibition for the prevention of AD are summarized in McDade et al., 2021.


    . The case for low-level BACE1 inhibition for the prevention of Alzheimer disease. Nat Rev Neurol. 2021 Nov;17(11):703-714. Epub 2021 Sep 21 PubMed.

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  1. APP A673T (Icelandic)


  1. Brain Biopsies and FinnGen Form Wellspring for Functional Genomics