FINE-STRUCTURE OF ABNORMAL FILAMENTS ISOLATED FROM ALZHEIMERS DISEASED BRAIN - AN APPLICATION OF ATOMIC-FORCE MICROSCOPY

Alzheimer's disease is characterized by the spontaneous assembly of a cytoskeletal protein into highly insoluble filamentous structures whic h appear, in conventional transmission electron microscopy (EM), as pa ired helical filaments (PHFs) or straight filaments (SFs). Recent exam ination of PHF ultrastructure using EM of vertical Pt-C replicas of is olated PHF indicate that PHFs more closely resemble twisted ribbons th an helically wound pairs of filaments. To re-evaluate the fine structu re of PHFs we isolated fractions highly enriched in PHF from Alzheimer diseased brains and characterized the fractions with an atomic force microscope. PHFs adhered to both mica and graphite surfaces without pr e-treatment of the surfaces and remained fixed to the substrate even a fter repeated scanning. Using the AFM, PHFs appeared as twisted ribbon s and had dimensions similar to those reported for vertically replicat ed PHF viewed with EM. Rare SFs were found admixed with typical twiste d ribbons. These data indicate that high resolution imaging using both Pt-C replication and AFM give similar quantitative data with respect to PHF dimensions. We conclude that Alzheimer PHFs should be modelled as a twisted ribbon rather than the structure implied by its name.