Seeding a conventional chemical oxidative polymerization of aniline with even very small amounts of biological, inorganic, or organic nanofibers (usually <1%) dramatically changes the morphology of the resulting doped electronic polymer polyaniline from nonfibrillar (particulate) to almost exclusively nanofibers. The nanoscale morphology of the original seed template is transcribed almost quantitatively to the bulk precipitate. These findings could have immediate impact in the design and development of high-surface area electronic materials.

We studied fibril formation in a family of peptides based on PHF6 (VQIVYK), a short peptide segment found in the microtubule binding region of tau protein. N-Acetylated peptides AcVYK-amide (AcVYK), AcIVYKamide (AcPHF4), AcQIVYK-amide (AcPHF5), and AcV-QIVYK-amide (AcPHF6) rapidly formed straight filaments in the presence of 0.15 M NaCl, each composed of two laterally aligned protofilaments ϳ5 nm in width. X-ray fiber diffraction showed the omnipresent sharp 4.7-Å reflection indicating that the scattering objects are likely elongated along the hydrogen-bonding direction in a cross-␤ conformation, and Fourier transform IR suggested the peptide chains were in a parallel (AcVYK, AcPHF6) or antiparallel (AcPHF4, AcPHF5) ␤-sheet configuration. The dipeptide N-acetyl-YK-amide (AcYK) formed globular structures ϳ200 nm to 1 m in diameter. The polymerization rate, as measured by thioflavin S binding, increased with the length of the peptide going from AcYK 3 AcPHF6, and peptides that aggregated most rapidly displayed CD spectra consistent with ␤-sheet structure. There was a 3-fold decrease in rate when Val was substituted for Ile or Gln, nearly a 10-fold decrease when Ala was substituted for Tyr, and an increase in polymerization rate when Glu was substituted for Lys. Twisted filaments, composed of four laterally aligned protofilaments (9 -19 nm width, ϳ90 nm halfperiodicity), were formed by mixing AcPHF6 with AcVYK. Taken together these results suggest that the core of PHF6 is localized at VYK, and the interaction between small amphiphilic segments of tau may initiate nucleation and lead to filaments displaying paired helical filament morphology.

Relative to the gray matter, there is a paucity of information regarding white matter biochemical alterations and their contribution to Alzheimer's disease (AD). Biochemical analyses of AD white matter combining size-exclusion, normal phase, and gas chromatography, immunoassays, and Western blotting revealed increased quantities of Abeta40 and Abeta42 in AD white matter accompanied by significant decreases in the amounts of myelin basic protein, myelin proteolipid protein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase. In addition, the AD white matter cholesterol levels were significantly decreased while total fatty acid content was increased. In some instances, these white matter biochemical alterations were correlated with patient apolipoprotein E genotype, Braak stage, and gender. Our observations suggest that extensive white matter axonal demyelination underlies Alzheimer's pathology, resulting in loss of capacitance and serious disturbances in nerve conduction, severely damaging brain function. These white matter alterations undoubtedly contribute to AD pathogenesis and may represent the combined effects of neuronal degeneration, microgliosis, oligodendrocyte injury, microcirculatory disease, and interstitial fluid stasis. To accurately assess the success of future therapeutic interventions, it is necessary to have a complete appreciation of the full scope and extent of AD pathology.