Sheep Offer New Insights into Alzheimer's Research

Alzheimer's disease is a big deal. It's a condition where the brain slowly breaks down. It's one of the toughest medical puzzles out there. Scientists have found that certain gene mutations can lead to early-onset Alzheimer's. These mutations are in the presenilin 1 and 2 (PSEN1 and PSEN2) and the amyloid precursor protein (APP) genes. These genes are crucial for the brain's functioning. They help create a complex called γ-secretase. This complex cuts up the APP to make different lengths of amyloid-beta (Aβ) peptides. Some of these peptides are longer and stick together to form plaques. These plaques are a big part of what makes Alzheimer's so harmful. Scientists wanted to see what happens when they tweak the PSEN1 gene. They created sheep with only one copy of the PSEN1 gene instead of two. This is called hemizygosity. Sheep are a good model for this kind of research. Their PSEN and APP genes are very similar to human genes. Plus, sheep naturally develop plaques and TAU tangles as they age, just like humans. At five years old, these modified sheep looked and acted normally. Their Aβ peptide levels in the cerebrospinal fluid and plasma were the same as regular sheep. This means that cutting PSEN1 levels in half didn't mess up the γ-secretase's job. So, just lowering PSEN1 levels might not be the magic bullet for treating Alzheimer's. However, it shows that losing one copy of PSEN1 might not hurt higher animals. This is important because there are people who naturally have only one copy of PSEN1 and they are fine. This opens up new paths for genetic therapies. Maybe knocking out or turning down one copy of PSEN1 could help prevent Alzheimer's caused by dominant mutations in PSEN1. It's a complex issue, but every bit of knowledge brings us closer to a solution.