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(American Journal of Pathology. 2000;156:797-805.)
© 2000 American Society for Investigative Pathology

Short Communications

Elevated Aß42 in Skeletal Muscle of Alzheimer Disease Patients Suggests Peripheral Alterations of AßPP Metabolism

Yu-Min Kuo^*, Tyler A. Kokjohn, M. Desiree Watson, Amina S. Woods^§, Robert J. Cotter^§, Lucia I. Sue^¶, Walter M. Kalback^*, Mark R. Emmerling, Thomas G. Beach^¶ and Alex E. Roher^*

From the Haldeman Laboratory for Alzheimer Disease Research^*
and the Civin Laboratory of Neuropathology,^¶
Sun Health Research Institute, Sun City, Arizona; the Department of Microbiology,
Midwestern University, Glendale, Arizona; the Department of Pharmacology and Molecular Sciences,^§
Johns Hopkins University School of Medicine, Baltimore, Maryland; and the Department of Neuroscience and Therapeutics,
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan

The levels of amyloid-ß40 (Aß40) and Aß42 peptides were quantified in temporalis muscles and brain of neuropathologically diagnosed Alzheimer disease (AD) and of nondemented individuals. This was achieved by using a novel analytical approach consisting of a combination of fast-performance liquid chromatographic (FPLC) size exclusion chromatography developed under denaturing conditions and europium immunoassay on the 4.0- to 4.5-kd fractions. In the temporalis muscles of the AD and nondemented control groups, the average values for Aß42 were 15.7 ng/g and 10.2 ng/g (P = 0.010), and for Aß40 they were 37.8 ng/g and 29.8 ng/g (P = 0.067), respectively. Multiple regression analyses of the AD and control combined populations indicated that 1) muscle Aß40 and muscle Aß42 levels were correlated with each other (P < 0.001), 2) muscle Aß40 levels were positively correlated with age (P = 0.036), and 3) muscle Aß42 levels were positively correlated with Braak stage (P = 0.042). Other forms of the Aß peptide were discovered by mass spectrometry, revealing the presence of Aß starting at residues 1, 6, 7, 9, 10, and 11 and ending at residues 40, 42, 44, 45, and 46. It is possible that in AD the skeletal muscle may contribute to the elevated plasma pool of Aß and thus indirectly to the amyloid deposits of the brain parenchyma and cerebral blood vessels. The increased levels of Aß in the temporalis muscles of AD patients suggest that alterations in AßPP and Aß metabolism may be manifested in peripheral tissues.

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