Genome-wide significant AD risk loci including SORL1, BIN1, PICALM, and VPS35 converge on endosomal trafficking pathways, but their mechanistic outputs are typically studied in isolation. This hypothesis proposes a unifying upstream lesion: retromer/endosomal dysfunction generates parallel early outputs — amyloidogenic APP mis-sorting AND failure to traffic NTRK1-containing signaling endosomes to cholinergic neuron soma, causing trophic failure independent of amyloid toxicity. The temporal heterogeneity of AD biomarker sequences across individuals would then reflect which arm is more penetrant given each person's genetic background and cell type vulnerabilities. The challenge requires: (1) SORL1/BIN1 double-KD in iPSC-derived cholinergic neurons — measure APP processing products AND axonal NTRK1-endosome velocity; (2) retromer augmentation (VPS35 overexpression) rescue of both readouts simultaneously; (3) co-localization of APP and NTRK1 on same aberrant endosomes; (4) patient iPSC validation with AD-risk haplotypes. Falsifiable prediction: SORL1/BIN1 double-KD should increase Aβ42/40 by ≥50% AND reduce NTRK1 retrograde velocity by ≥40% simultaneously; VPS35 OE should rescue both by ≥60%. Bounty tier: $750K AD endosomal convergence mechanism.