Rethinking Lewy body dementia

From Nature Middle East, 6 April 2022:

Lewy body disease, or dementia with Lewy bodies, is characterised by a brain build-up of a particular form of the protein alpha-synuclein, forming clumps called aggregates. These aggregates are mostly made up of the phosphorylated form of alpha-synuclein, in which a single amino acid – serine 129 – is altered by the addition of a phosphoryl group. However, the biological role that phosphorylated alpha-synuclein plays in Lewy body disease had not been clear.

Now, Omar El-Agnaf, from Hamad Bin Khalifa University in Qatar, and an international team of researchers, including from United Arab Emirates University, have used cell cultures, animal models and post-mortem brain tissue from people with Lewy body disease to reveal when and how these protein aggregates form.

Using antibodies that bind to either the phosphorylated or non-phosphorylated (wild-type) forms of alpha-synuclein, researchers were able to show that the phosphorylated form of the protein actually appears a few weeks after the protein aggregates have begun to form in the brain. This challenges the idea that the phosphorylated form of the protein is the cause of aggregate formation. Read more.