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New Patterns of Intraneuronal Accumulation of the Microtubular Binding Domain of tau in Granulovacuolar Degeneration

Department of Pharmacology and Therapeutics (Drs Mena and Cuello), McGill University, McIntyre Medical Sciences Building, Montreal and the Brain Bank (Dr Robitaille), Douglas Hospital Research Center, Verdum, Quebec, Canada.

Yves Robitaille, MD

Department of Pharmacology and Therapeutics (Drs Mena and Cuello), McGill University, McIntyre Medical Sciences Building, Montreal and the Brain Bank (Dr Robitaille), Douglas Hospital Research Center, Verdum, Quebec, Canada.

A. Claudio Cuello, MD, DSc

Department of Pharmacology and Therapeutics (Drs Mena and Cuello), McGill University, McIntyre Medical Sciences Building, Montreal and the Brain Bank (Dr Robitaille), Douglas Hospital Research Center, Verdum, Quebec, Canada.

Sixteen brains from Alzheimer's disease (AD) patients with varying duration of dementia were studied using the monoclonal antibody (mAb) 6.423 raised against the three repeated domains of the tau protein, and named the paired helical filament (PHF) core. In Ammon's horns of the AD cases 6.423 mAb, in addition to immunoreacting with neurofibrillary tangles (NFTs), dystrophic neurites, and plaquelike structures, also recognized a subpopulation of granulovacuolar degeneration elements (GVD). A new immunoreactive structure, a spherical inclusion, was also stained by 6.423. The immunoreactive GVD elements and the spherical inclusion were found in the aged controls (> 65 years of age) and in non-AD dementia cases, as well. The staining of the GVD was markedly decreased when the tissue was preincubated with alkaline phosphatase. In contrast, NFTs and the spherical inclusions resisted dephosphorylation. Neurons containing the spherical inclusion frequently lacked immunoreactive intracellular NFTs. Due to the similar immunohistochemical properties between the spherical bodies and immunoreactive NFTs, we named this new inclusion PHF core body. Our results suggest that the PHF core body may represent a successful attempt by hippocampal neurons to restrict the PHF core expression. Thus, the failure of this mechanism may lead to the NFT formation in a range of dementing processes. Alternatively, the PHF core body may be an early stage in the NFT formation. (J Geriatr Psychiatry Neurol 1992;5:132–141).

Journal of Geriatric Psychiatry and Neurology, Vol. 5, No. 3, 132-141 (1992)
DOI: 10.1177/002383099200500302


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