This study presents cryo-electron microscopy (cryo-EM) maps and atomic models of paired helical filaments (PHFs) and straight filaments (SFs) of Tau proteins from the brains of patients with Alzheimer's disease (AD). The filaments are composed of two identical protofilaments, each comprising residues 306–378 of Tau, which adopt a combined cross-β/β-helix structure. PHFs and SFs differ in their interprotofilament packing, demonstrating that they are ultrastructural polymorphs. The findings highlight the potential of cryo-EM for atomic characterization of amyloid filaments from patient-derived material, advancing the understanding of neurodegenerative diseases. The study also discusses the implications of these structures for the propagation of neurofibrillary lesions in AD and the development of specific inhibitors and tracers for Tau aggregation.This study presents cryo-electron microscopy (cryo-EM) maps and atomic models of paired helical filaments (PHFs) and straight filaments (SFs) of Tau proteins from the brains of patients with Alzheimer's disease (AD). The filaments are composed of two identical protofilaments, each comprising residues 306–378 of Tau, which adopt a combined cross-β/β-helix structure. PHFs and SFs differ in their interprotofilament packing, demonstrating that they are ultrastructural polymorphs. The findings highlight the potential of cryo-EM for atomic characterization of amyloid filaments from patient-derived material, advancing the understanding of neurodegenerative diseases. The study also discusses the implications of these structures for the propagation of neurofibrillary lesions in AD and the development of specific inhibitors and tracers for Tau aggregation.