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Regional and Laminar Distribution of Neurofibrillary Tangles and Senile Plaques

Patrick R. Hof, MD; Linda M. Bierer, MD; Daniel P. Perl, MD; André Delacourte, PhD; Luc Buée, MSc; Constantin Bouras, MD; John H. Morrison, PhD

Arch Neurol. 1992;49(9):946-953.

Abstract
• Detailed neuropathologic studies of neurofibrillary tangle and senile plaque distribution have shown that key elements of certain neocortical and hippocampal circuits are either compromised or lost in Alzheimer's disease. It has been suggested that a global corticocortical disconnection underlies dementia and leads to the dramatic disruption of integrated functions exhibited by patients with Alzheimer's disease. To investigate the distribution of lesions associated with the earliest indications of incipient dementia, we performed a quantitative neuropathologic evaluation of a nondemented 82-year-old patient demonstrating globally intact intellectual function but initial signs of impairment of specific cognitive functions before death. We observed densities of senile plaques comparable to those found in Alzheimer's disease throughout the cerebral cortex, whereas extensive neurofibrillary tangle formation was restricted to selective areas of the temporal lobe. The results of this systematic quantitative and comparative analysis of medial and inferior temporal lobe structures suggest a functional relationship between the degree of cognitive decline evidenced in the earliest stages of Alzheimer's disease and the anatomic progression of Alzheimer's disease-related pathologic changes along specific elements of the cortical circuitry.

Author Affiliations
From the Fishberg Research Center for Neurobiology (Drs Hof, Perl, and Morrison), the Department of Geriatrics and Adult Development (Drs Hof, Delacourte, and Morrison and Mr Buée), the Department of Pathology (Dr Perl), and the Department of Psychiatry (Drs Bierer and Perl), Mount Sinai School of Medicine, New York, NY; INSERM Unité 156, Lille, France (Dr Delacourte and Mr Buée); and the Department of Psychiatry, University of Geneva (Switzerland) School of Medicine (Dr Bouras).

Footnotes
Accepted for publication April 27, 1992.

Reprint requests to the Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, Box 1065, One Gustave L. Levy Place, New York, NY 10029 (Dr Hof).

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