Alzheimer paired helical filaments (PHFs) studied by high-resolution TEM: What can vertical Pt-C replication tell us about the organization of the pronase-digested PHF core?

Untreated paired helical filaments (PHFs) and pronase‐digested PHF‐core filaments were stereoscopically imaged with a freeze‐drying vertical platinum‐carbon replication preparation method for TEM. The untreated PHF have an average wide region (W) = 22.8 ± 2.4 nm, a narrow region (T) = 10.6 ± 1.7 nm, and a helical turn period (L) = 78.6 ± 13.4. The surfaces of the untreated PHF's fuzzy coat appears disorganized. The widths of the pronase‐treated PHF‐core filaments were significantly reduced (Wd = 14.8 ± 1.2 nm, Td = 5.7 ± 1.0 nm, and Ld = 75.4 ± 17 nm). The surfaces of the untreated PHF contained ∼1.1 nm strands, the same size as tau monomer (∼1.0 nm). The pronase‐digested PHF cores mostly contained ∼1.6 ± 0.3 nm strands although strand diameters ranged from 0.6–2.5 nm. The strands sometimes appear to be wrapped around the filament axis; less often, they appear to be roughly parallel to the PHF axis, and otherwise appear to be randomly oriented. Images of pronase‐digested PHF core images are discussed in relation to the core's biochemical composition, its proposed beta structure, and structural subunit models. Images of the untreated and the pronase‐digested PHF support a helical ribbon morphology. Microsc. Res. Tech. 67:196–209, 2005. © 2005 Wiley‐Liss, Inc.