Network abnormalities and interneuron dysfunction in Alzheimer disease

Key Points The brain controls the function of neural circuits and networks, in part, by modulating the synchrony of their components. Network hypersynchrony and altered oscillatory rhythmic activity may underlie cognitive abnormalities in Alzheimer disease (AD). In AD, network activities that support cognition are altered decades before clinical disease onset, and the affected networks predict future pathology and brain atrophy. Although the precise causes and pathophysiological consequences of these network alterations remain to be fully elucidated, interneuron dysfunction and network abnormalities have emerged as potential mechanisms of cognitive dysfunction in AD and related disorders. Several lines of evidence suggest that modulating interneuron-dependent network alterations could be a useful therapeutic strategy to improve brain functions in these conditions. The cognitive abnormalities observed in Alzheimer disease (AD) may be linked to alterations in oscillatory rhythmic activity and neuronal network hypersynchrony. Palop and Mucke review these links and explore how countering these network abnormalities and interneuron dysfunction may hold therapeutic potential for AD. The function of neural circuits and networks can be controlled, in part, by modulating the synchrony of their components' activities. Network hypersynchrony and altered oscillatory rhythmic activity may contribute to cognitive abnormalities in Alzheimer disease (AD). In this condition, network activities that support cognition are altered decades before clinical disease onset, and these alterations predict future pathology and brain atrophy. Although the precise causes and pathophysiological consequences of these network alterations remain to be defined, interneuron dysfunction and network abnormalities have emerged as potential mechanisms of cognitive dysfunction in AD and related disorders. Here, we explore the concept that modulating these mechanisms may help to improve brain function in these conditions.