Elevated Aβ42 in skeletal muscle of Alzheimer disease patients suggests peripheral alterations of AβPP metabolism

The levels of amyloid-beta 40 (A beta 40) and A beta 42 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 A beta 42 were 15.7 ng/g and 10.2 ng/g (P = 0.010), and for A beta 40 they were 37.8 ng/g and 23.8 ng/g (P = 0.067), respectively, Multiple regression analyses of the AD and control combined populations indicated that 1) muscle A beta 40 and muscle A beta 42 levels were correlated with each other (P < 0.001), 2) muscle A beta 40 levels were positively correlated with age (P = 0.036), and 3) muscle A beta 42 levels were positively correlated with Braak stage (P = 0.042). Other forms of the A beta peptide were discovered by mass spectrometry, revealing the presence of A beta 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 con tribute to the elevated plasma pool of A beta and thus indirectly to the amyloid deposits of the brain parenchyma and cerebral blood vessels. The increased levels of A beta in the temporalis muscles of AD patients suggest that alterations in A beta PP and A beta metabolism may be manifested in peripheral tissues.