With the advent of new omics technologies, in the past few years, there has been a deluge of complex, high-dimensional data on Alzheimer's disease (AD). In particular, single-nucleus technologies have begun to unveil the molecular underpinnings of various brain cell-types and states, their response to AD pathology, and the interactions among them [1]. To date, several bulk and single-nucleus transcriptomics studies on AD have been published that identify cell-specific molecular disruptions observed in AD and the intricate interactions among the various brain cell types [2-5]. In addition, several more studies on proteomics, metabolomics, epigenomics, and genetics have shed light on the complex pathophysiological landscape of AD [6][7][8][9][10]. Moreover, data that shed light on the spatial relationships of brain cells with AD pathology is also being generated [11,12]. The current supplemental issue is a topical collection to provide new insights into altered pathways and disease-related processes, increasing our understanding of AD pathogenesis to identify specific biomarkers of disease status, progression, or therapeutic response.The research articles featured in this issue encompass several themes. The first theme is the molecular and cellular mechanisms underlying AD. Chum et