Brain cells called oligodendrocytes are a key source of amyloid beta (Aβ) and play a crucial role in causing nerve cell dysfunction in Alzheimer’s disease (AD), as per a study published on July 23, 2024, in the journal PLOS Biology by Rikesh Rajani and Marc Aurel Busche from the UK Dementia Research Institute at University College London, along with other researchers.
AD is a severe degenerative brain disease affecting millions worldwide. The buildup of Aβ, which are peptides made up of 36 to 43 amino acids, is one of the earliest critical signs of the disease. Recent research trials have shown that treating individuals with AD using anti-Aβ antibodies can slow down cognitive decline, underscoring Aβ’s significant role in the disease process. Despite the well-known effects of Aβ on cells and its importance in AD, the common belief that nerve cells are the primary source of harmful Aβ in the brain had not been investigated until now.
The study by Rajani and Busche revealed that oligodendrocytes, non-nerve brain cells, are responsible for producing Aβ. They also proved that reducing Aβ production specifically in oligodendrocytes in an AD mouse model can improve abnormal nerve cell activity. These results highlight the essential role of oligodendrocyte-produced Aβ in causing early nerve cell dysfunction in AD. This suggests that targeting Aβ production in oligodendrocytes could be a promising approach for AD treatment.
Despite the relatively small reduction in plaque formation when oligodendrocyte Aβ production is blocked compared to blocking nerve cell Aβ production, the functional improvement is significant. This indicates that oligodendrocyte-generated Aβ likely plays a crucial role in causing nerve cell dysfunction, rather than directly affecting plaque buildup. The study also found an increased number of Aβ-producing oligodendrocytes in deeper brain layers of individuals with AD, suggesting a key role for these cells in early nerve circuit dysfunction in AD, influencing disease progression and treatment approaches. The higher presence of oligodendrocytes in AD brains raises the possibility that they could compensate for reduced Aβ production as nerve cell loss occurs during disease progression.
The researchers stated, “Our research challenges the conventional view that nerve cells are the sole source of amyloid beta in the brain, one of the harmful proteins that accumulates in Alzheimer’s Disease. We have shown that oligodendrocytes, the cells that produce myelin in the central nervous system, can also generate significant amounts of amyloid beta, leading to nerve cell dysfunction. This finding suggests that targeting these cells could be a new and promising strategy for treating Alzheimer’s Disease.”
