Tau immunoreactivity was studied in temporal neocortex, area 22, in 15 cases with graded intellectual status and compared with the immunoreactivity observed with an antiserum against paired helical filaments (PHF) and with the density of amyloid revealed by thioflavin S. Samples came from women over 75 years either intellectually normal or affected by senile dementia of the alzheimer type at various degrees of severity. Mental status had been prospectively assessed by the Blessed's test score. Antitau labelled a neuropil meshwork, the density of which increased with the severity of the disease. This meshwork was denser in layers II, III and V in the most affected cases. The number and the size of the taupositive fibers within the senile plaques increased with the intellectual deficit. Senile plaques were more numerous in layers II and III and neurofibrillary tangles in layers III and V whatever the staining technique: tau or PHF immunocytochemistry, and thioflavin S. The densities of senile plaques and of neurofibrillary tangles (NFT) were correlated with the severity of the disease whatever the staining method. The three methods revealed a systematically different number of changes. This systematic difference could greatly influence the neuropathological diagnosis. It could be the consequence of various factors: different sensitivities of the staining methods or changes in the antigenic and amyloid composition of the lesion according to the stage of the disease. In line with the last hypothesis, a higher proportion of amyloid-rich plaques was noted in the less affected cases, suggesting that tau and PHF epitopes appeared secondarily. Tau epitopes seemed to be present at least as early as PHF epitopes in the NFT. The pathological changes best linked to dementia were NFT revealed by tau antiserum.

/pdf/tau-paired-helical-filaments-and-amyloid-in-the-neocortex-a-zm5zvakch2.pdf

Tau, paired helical filaments and amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in aging and senile dementia of Alzheimer type

Alzheimer's disease and related conditions

The cytoskeleton of a normal mature neuron is composed of three types of fibrils, the microtubules, the neurofilaments and the microfilaments. One of the cellular and molecular changes with aging, the mechanism of which remains unknown to date, is the formation of argentophilic intracellular neurofibrillary tangles in certain selected neurons of the aged human brain. These extraordinary neurofibrillary changes are seen in great abundance in several adult and late life dementias especially the Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT) (for review see Iqbal, et al. 1977b; Iqbal and Wisniewski 1983). The Alzheimer neurofibrillary tangles (ANT) are composed of paired helical filaments (PHF). Bundles of these PHF are also found in neurites (Braak, et al. 1986), especially in the dystrophic neurites of the neuritic (senile) plaque, the second leading histopathological lesion of AD/SDAT. Together these two lesions, the ANT and the plaques, both of which contain the PHF, are the histopathological hallmark of AD/SDAT (Kidd, 1964; Terry, et al. 1964); occassionally either tangles of 15 nm straight filaments or these filaments admixed with PHF have been observed in a few AD/SDAT cases. (Shibayama and Kitoch, 1978; Yagishita, et. al. 1981). The number of ANT and plaques correlates positively with the degree of psychometric deficiency in the affected patients (Tomlinson, et. al. 1970), but their origin and role in disease are not understood.

Alterations of the Neuronal Cytoskeleton in Alzheimer’s Disease and Related Conditions

The mental status of 15 women over 75 years, either intellectually normal of affected by senile dementia of the Alzheimer type at various degrees of severity, was assessed prospectively by Blessed’s test score. The pattern and density of tau immunoreactivity were studied in temporal neocortex area 22, and compared with those of PHF immunoreactivity and with the density of amyloid revealed by thio-flavin S.

Relationship Between Tau, Paired Helical Filaments, Amyloid and the Intellectual Deterioration in the Neocortex in Normal Aging and in Senile Dementia of the Alzheimer Type

Biology of Alzheimer's disease through biochemistry of tangles and plaques

Neurofibrillary tangles of Alzheimer's disease.: Ultrastructural and immunohistochemical study.

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Neurofibrillary tangles of Alzheimer's disease.: Ultrastructural and immunohistochemical study.