Elevated Aβ42 in skeletal muscle of Alzheimer disease patients suggests peripheral alterations of AβPP 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, Alex E. Roher

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

Abstract

The levels of amyloid-β40 (Aβ40) and Aβ42 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 Aβ42 were 15.7 ng/g and 10.2 ng/g (P = 0.010), and for Aβ40 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 Aβ40 and muscle Aβ42 levels were correlated with each other (P < 0.001), 2) muscle Aβ40 levels were positively correlated with age (P = 0.036), and 3) muscle Aβ42 levels were positively correlated with Braak stage (P = 0.042). Other forms of the Aβ peptide were discovered by mass spectrometry, revealing the presence of Aβ 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 Aβ and thus indirectly to the amyloid deposits of the brain parenchyma and cerebral blood vessels. The increased levels of Aβ in the temporalis muscles of AD patients suggest that alterations in AβPP and Aβ metabolism may be manifested in peripheral tissues.

Original languageEnglish
Article number64947
Pages (from-to)797-805
Number of pages9
JournalAmerican Journal of Pathology
Volume156
Issue number3
DOIs
Publication statusPublished - 2000 Mar

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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