Progressive supranuclear palsy: extensive neuropil threads in addition to neurofibrillary tangles

Abstract

Light microscopic immunohistochemical investigations were performed on neurofibrillary tangles (NFT) in four histologically confirmed cases of Alzheimer's disease (AD) and in five patients with a progressive supranuclear palsy (PSP). The antibody panel included antisera to the neuronal microtubule-associated protein, tau, and to isolated paired helical filaments (PHF), as well as mouse monoclonal antibodies (MAbs) to phosphorylated epitopes on high and medium molecular weight neurofilament subunits (RT97 and BF10, respectively). Paraffin sections were also impregnated with the Gallyas silver method, which specifically stains tangles and cortical neuropil threads in AD, but does not stain normal neurofilaments. All tangles in PSP and AD showed consistent immunostaining with antibodies to tau protein and isolated PHF, regardless of their localization. MAbs RT97 and BF10, however, did not stain or only weakly stained, subcortical tangles in PSP and AD, whereas most cortical NFT in AD were intensely immunostained. All tangles in PSP were as heavily impregnated with Gallyas as they were in AD. Furthermore there were extensive networks of Gallyas-positive, tau- and PHF-immunoreactive neurites in subcortical gray areas containing NFT, and bundles of positive axons in white matter tracts interconnecting subcortical nuclei of PSP. Our studies indicate a much more extensive disruption of fibrillar proteins in PSP subcortical neurons than previously reported. They furthermore indicate a very similar antigenic profile of NFT in PSP and AD, as far as subcortical neurons are concerned.

Relationship of Complement-Activated Oligodendrocytes to Reactive Microglia and Neuronal Pathology in Neurodegenerative Disease

“…Both the antibody to ubiquitin and Alz50 appeared to stain the neuropil threads or grains. These are well known in AD and have also been reported in progressive supranuclear palsy [ 17] and subacute sclerosing panencephalitic brains [18]. We have also found widespread thread and grain formation in the brains of persons with ArGD, and in somewhat less abundant numbers in affected regions in Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS).…”

Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.

“…The most frequent form of dystrophic neurites in AD are neuropil threads that are not confined to the SP (14). Furthermore, neuropil threads are also found in progressive supranuclear palsy (15) and subacute sclerosing panencephalitis (16) in the absence of 8-AP deposits. Neuritic SP contain dystrophic neurites that accumulate paired helical filaments and membranous dense bodies (17).…”

Cognitive impairment in Parkinson's disease: amyloid plaques, neurofibrillary tangles, and neuropil threads in the cerebral cortex

“…They contribute a substantial amount to the total of neurofibrillary changes (Probst et al, 1988;Braak et al, 1989 a) and, occasionally, aquire such a density to permit the delineation of architectonic units (e.g. extent of the dendritic trees of Pre-a neurons; extent of layer V in the striate area: Braak et al, 1989a).…”