The framework and composition of AG stroma change with age. (A) Fluorescent images of AG, shown at intermediate power from young, middle-aged, and old individuals demonstrate collagen-enrichment within stromal cores. (B) Ingrowth of capsular elements is more pronounced in older individuals, as demonstrated in a plot depicting percent label of arachnoid markers in capsule and core regions according to age. (C) Enlarged cropped images of the core show collagen arrangement into fibrillar and trabecular patterns, which give rise to internal sinus and crypt spaces. (D) The AG core composite is summarized based on percent stromal label in an age-coded barycentric plot and illustrates the diminishment of collagen and enhancement of space content with age. (E–H) Cavernous space immune cells are shown in confocal (E), 3D CLARITY (F), TEM (G), and schematic (H) images. (I and J) Quantification of DAPI label in vimentin− AG core regions is shown in all, young, middle-aged, and old persons (I), and presence of immune cells (i.e., the fraction of AG positive for marker) is shown in J. (K) TNF label within sinuses and crypts is further demonstrated in AG from young, middle-aged, and old decedents. (L) Semiquantitative cytokine and immune label results are summarized. (A, C, E, F, and K) Green/FITC, vimentin, CD68, or TNF; red/CY3, pan-collagen; cyan/CY5, fibronectin; blue, DAPI. Scale bars: (A) 50 μm; (C) 20 μm; (E, F, G, and K) 10 μm. The asterisks (*) in C denote sinus spaces. Data represent findings in 400 frontal pole granulations from 20 decedents and are from more than two independent experiments.