Increased Amount Of Enzyme In Brain May Be Marker Of Alzheimer's Disease

December 29, 1997

CHICAGO --- An enzyme present in extremely low quantities in normal brains has been found to be greatly increased in the brains of patients with Alzheimer's disease.

Alzheimer's disease researcher M.-Marsel Mesulam, M.D., and colleagues at Northwestern University Medical School found that the enzyme, butyrylcholinesterase (BChE), increases at the stage when beta-amyloid plaques in the brain become compact and insoluble. These insoluble beta-amyloid plaques are one of two early pathological markers of Alzheimer's disease.

A report of the group's findings appears in the December issue of the Annals of Neurology. Their results suggest that BChE may help transform benign amyloid protein deposits in the brain into the compact plaques associated with the nerve degeneration and dementia of Alzheimer's disease.

Mesulam is the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Science, a professor of neurology and the director of the behavioral and cognitive neurology and Alzheimer's disease program at Northwestern.

In this study, he and his colleagues tested brain tissue specimens from two persons with Alzheimer's disease and specimens from four non-demented persons for the presence of BChE and its confirming markers. Their results showed that only the compact and neuritic forms of amyloid plaques had BChE. (It is this neuritic stage that is most closely associated with Alzheimer's disease-related dementia.) Many amyloid deposits that consisted almost entirely of diffuse plaques were found in tissue from non-demented subjects. BChE was therefore a better marker than amyloid for differentiating normal aging from Alzheimer's disease.

Mesulam and other investigators have shown that deposits of diffuse (and harmless) beta-amyloid may exist in the brain for many years before leading to Alzheimer's dementia.

The factors that contribute to the transformation of the beta-amyloid from a relatively inert to a disease-causing state remain unknown and may involve interactions with additional plaque constituents, he said.

Among these constituents are a number of "companion" molecules, e.g., apolipoprotein E, complement factors, acetylcholinesterase, BChE and others. Mesulam and colleagues believe that some of these companion molecules could conceivably influence the transformation of the plaque from a benign to a malignant form.

"One potential pattern for such a companion molecule would be to have a preferential association with the mature rather than early stages of amyloid plaques," Mesulam said.

Of all the companion molecules associated with beta-amyloid, only BChE is present at the later but not the initial stages of plaque maturation.

"Our evidence suggest that BChE probably is inserted into the amyloid plaque at an advanced stage of maturation, at a time when the plaque is becoming associated with pathogenic properties," Mesulam said.

Other investigators on this study were Angela L. Guillozet and John F. Smiley, research assistant professor of neurology, Northwestern University Medical School, and D.C. Mash, department of neurology, University of Miami School of Medicine, Miami, Fla.

(Editor's note: Dr. Mesulam can be reached at 312-908-9339 or by e-mail at

Northwestern University

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