It may seem counter intuitive, but could BACE2 protect against amyloidosis, rather than contribute to it? This is the central question in a manuscript posted to bioRxiv. Non-amyloidogenic processing of APP, and Aβ peptides, by BACE2 may counteract the effect of an extra copy of APP in some people with Down’s syndrome, the authors propose.
Led by Dean Nižetić, Queen Mary University, London, Henrik Zetterberg, University of Gothenburg, Sweden, and John Hardy, University College London, scientists found that brain organoids derived from skin cells donated by people with Down’s secrete truncated Aβ peptides. They are cleaved at amino acids 19, 20, and 34—all previously proposed BACE2 cleavage sites. Cerebrospinal fluid from people with Down’s also has more of these truncated peptides than does control CSF, the researchers report. These forms of Aβ are not amyloidogenic.
- BACE2 can cut APP at Aβ position 19, in non-amyloidogenic fashion.
- It can also cleave Aβ peptides at amino acids 20 and 34.
- Down syndrome CSF/brain organoids contain more of these truncated Aβ peptides.
Read the full report on the Alz Forum Website – https://www.alzforum.org/news/research-news/can-bace2-protect-against-amyloidosis