Ms. Pollanen et al., FINE-STRUCTURE OF ABNORMAL FILAMENTS ISOLATED FROM ALZHEIMERS DISEASED BRAIN - AN APPLICATION OF ATOMIC-FORCE MICROSCOPY, Colloids and surfaces. A, Physicochemical and engineering aspects, 87(3), 1994, pp. 213-216
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.