Using ultrasensitive single-aggregate imaging techniques (Horrocks et al., 2016; Whiten et al., 2018b) and lipid permeabilization assays (Flagmeier et al., 2017) capable of characterizing the low concentration of secreted aggregates, we show that long-term treatment with TNF substantially increases the production of biologically active Aβ and α-synuclein-containing aggregates specifically in compromised familial Alzheimer’s disease neurons, but not healthy neurons, suggestive of a role for inflammation in early Alzheimer’s disease pathology. This evidence concerns the gene TNF and early-onset autosomal dominant Alzheimer disease.