A Progressive Deposition of Paired Helical Filaments (PHF) in the Brain Characterizes the Evolution of Dementia in Alzheimerʼs Disease.

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Abstract
Using the monoclonal antibody (mAb) 6.423 which recognizes epitopes of the pronase-resistant core of paired helical filaments (PHF), we studied postmortem frontal cortex from Alzheimer's disease (AD) patients with short (Group II) and long (Group III) histories of clinical dementia. Four cases with clinically unconfirmed dementia and a postmortem diagnosis of AD (Group I) were also studied. In Group I, the 6.423 mAb was negative whereas in Group II, the antibody recognized primarily neurofibrillary tangles (NFT). In contrast, brains in Group III contained a dense network of 6.423-immunoreactive (IR) thread-like structures (“ghost” neurites) and plaque-like structures with granular appearance, in addition to NFT. The number of 6.423-IR structures appeared to be related to the duration of clinical dementia and the age of onset. Furthermore, “ghost” neurites were more abundant in young AD cases. The possible significance of the 6.423-IR pattern in the pathogenesis of AD is discussed

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