Journal of Neuroscience, Vol 11, 1748-1755, Copyright © 1991 by Society for Neuroscience
Neuropil threads of Alzheimer's disease show a marked alteration of the normal cytoskeleton
G Perry, M Kawai, M Tabaton, M Onorato, P Mulvihill, P Richey, A Morandi, JA Connolly and P Gambetti
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
Abnormal neurites, neuropil threads, are a widespread and characteristic
lesion of Alzheimer's disease likely to play a major role in the cognitive
impairment of this disease. Contrary to normal neurites, neuropil threads
contain straight and paired helical filaments that contain the
microtubule-associated protein tau and ubiquitin. It is not known whether
these abnormal filaments are added to or replace the normal cytoskeleton.
In this study, we examined the fine structure of neuropil threads and
carried out a morphometric analysis of the neurofilaments and abnormal
filaments contained in the neuropil threads by using an antiserum to tau
and colloidal gold immuno- electron microscopy. Almost 70% of the neuropil
threads contained straight or paired helical filaments with no
neurofilaments. The total number of filaments in each neuropil thread
remained essentially unchanged either when straight or paired helical
filaments were present alone or when they coexisted either together or with
neurofilaments. When the three types of filaments were expressed as a
proportion of the total, a linear inverse correlation was found between
neurofilaments and straight filaments as well as between straight and
paired helical filaments. Approximately 10% of the neuropil threads were
found to be myelinated axons. It is concluded that straight filaments are
likely to replace neurofilaments, that they in turn might be replaced by
paired helical filaments, and that this process occurs in axons as well as
dendrites.
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