Fontana_2023_Nat.Rev.Neurol__

The ongoing search for therapeutic interventions in Alzheimer disease (AD) has highlighted the complexity of this condition and the need for additional biomarkers, beyond amyloid-beta (Abeta) and tau, to improve clinical assessment. Astrocytes are brain cells that control metabolic and redox homeostasis, among other functions, and are emerging as an important focus of AD research owing to their swift response to brain pathology in the initial stages of the disease. Reactive astrogliosis - the morphological, molecular and functional transformation of astrocytes during disease - has been implicated in AD progression, and the definition of new astrocytic biomarkers could help to deepen our understanding of reactive astrogliosis along the AD continuum. As we highlight in this Review, one promising biomarker candidate is the astrocytic alpha7 nicotinic acetylcholine receptor (alpha7nAChR), upregulation of which correlates with Abeta pathology in the brain of individuals with AD. We revisit the past two decades of research into astrocytic alpha7nAChRs to shed light on their roles in the context of AD pathology and biomarkers. We discuss the involvement of astrocytic alpha7nAChRs in the instigation and potentiation of early Abeta pathology and explore their potential as a target for future reactive astrocyte-based therapeutics and imaging biomarkers in AD.