Oligodendrocytes are an important source of amyloid beta (Aβ) and play a key role in promoting neuronal dysfunction in Alzheimer's disease (AD), according to a study published July 23, 2024 in the open-access journal PLOS Biology by Rikesh Rajani and Marc Aurel Busche from the UK Dementia Research Institute at University College London, and colleagues. AD is a devastating neurodegenerative disorder affecting millions of people worldwide. Accumulation of Aβ – peptides consisting of 36 to 43 amino acids – is an early critical hallmark of the disease.
Recent clinical trials demonstrating a slowing of cognitive and functional decline in individuals with AD who are treated with anti-Aβ antibodies reinforce the important role of Aβ in the disease process. Despite the key cellular effects of Aβ and its essential role in AD, the traditional assumption that neurons are the primary source of toxic Aβ in the brain has remained untested. In the study, Rajani and Busche showed that non-neuronal brain cells called oligodendrocytes produce Aβ.
They further demonstrated that selectively suppressing Aβ production in oligodendrocytes in an AD mouse model is sufficient to rescue abnormal neuronal hyperactivity. The results provide evidence for a critical role of oligodendrocyte-derived Aβ for early neuronal dysfunction in AD. Collectively, the findings suggest that targeting oligodendrocyte Aβ production could be a promising therapeutic strategy for treating AD.
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