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Jay W. Pettegrew, MD; Kanagasabai Panchalingam, PhD; John Moossy, MD; Julio Martinez, MD; Gutti Rao, MD; Francois Boller, MD

Arch Neurol. 1988;45(10):1093-1096.

Abstract
• Senile plaques (SPs), especially, and neurofibrillary tangles are important pathologic markers for the diagnosis of Alzheimer's disease (AD), but neither is pathognomonic for AD. We hypothesize that elevations in levels of phosphomonoesters, precursors of membrane phospholipids, occur early in the pathogenesis of AD and precede the appearance of SPs. In contrast, elevations in levels of phosphodiesters, breakdown products of phospholipids, reflect degeneration of neural membranes and will correlate with the appearance of SPs. Correlative phosphorus-31 magnetic resonance spectroscopy and morphologic studies conducted to test this hypothesis disclosed that elevations in levels of phosphomonoesters had a negative correlation with the numbers of SPs, and elevations in levels of phosphodiesters had a positive correlation with the numbers of SPs. No correlations were observed for either membrane parameter and neurofibrillary tangles. These findings support our hypothesis and suggest that aberrations in the synthesis of membrane phospholipids are early metabolic events in the pathogenesis of AD.

Author Affiliations
From the Departments of Psychiatry (Drs Pettegrew and Panchalingam), Neurology (Drs Pettegrew, Moossy, and Boller), and Pathology (Drs Moossy, Martinez, and Rao), University of Pittsburgh.

Footnotes
Accepted for publication May 20, 1988.

Reprint requests to University of Pittsburgh, Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213 (Dr Pettegrew).

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