Evaluation of skeletal muscle oxidative metabolism in Alzheimer disease

Aim: Recently evidence has been provided that Beta-amyloid (bAP) deposits, the pathogenetic feature of Alzheimer disease (AD) [1, 2], can be also present in the mitochondria of skeletal muscle cells [3]. The aim of this study was to evaluate whether in AD patients bAP deposits in skeletal muscle impair oxidative metabolism. Methods: Thirteen AD patients (73.5 ± 1.0 years, mean ± SD) and twenty-nine healthy sex-matched control subjects (CTRL) (73.3 ± 1.1 years) were investigated. Two incremental exercise until voluntary exhaustion were performed, in order to evaluate skeletal muscle oxidative metabolism: a cycloergometer (CE) and a one-leg knee extension (KE) exercise. The following variables were determined: breath-by-breath pulmonary O2 uptake (VO2); heart rate (HR); cardiac output (CO); vastus lateralis muscle fractional O2 extraction by near-infrared spectroscopy (D[deoxy(Hb ± Mb)]); blood lactate concentration ([La-]) at rest and after exercise; maximal voluntary contraction (MVC); total daily energy expenditure (TEE). Results: During CE, peak work-rate (94.1 ± 7.1 vs. 128.3 ± 8.5 watt) and VO2 peak (22.0 ± 0.8 vs. 26.4 ± 1.1 mL kg-1 min-1) were significantly lower in AD patients vs. CTRL. CO was similar between AD patients (14.4 ± 0.5 L min-1) and CTRL (15.3 ± 0.9 L min-1) whereas D[deoxy(Hb ± Mb)] was significantly lower in AD patients (51.05 ± 5.8 %) vs. CTRL (71.4 ± 2.9 %). During KE, VO2 peak (10.7 ± 0.7) vs. 13.5 ± 0.6 mL kg-1 min-1) and D[deoxy(Hb ± Mb)] (40.02 ± 5.8 vs. 61.01 ± 4.7 %) were significantly lower in AD patients vs. CTRL. CO (10.93 ± 0.5 vs. 11.62 ± 0.9) and [La-] were not significantly different between AD and CTRL. TEE was similar in AD and CTRL (2,534 ± 243.6 vs. 2,250 ± 119.3 kcal day-1). As for MVC, no significant difference was found between CTRL and AD (440.5 ± 39.5 N vs. 438.3 ± 86.7 N, respectively). Conclusion: Data from the present study indicate that AD patients have a reduced exercise capacity compared to healthy control subjects, probably due to a reduced muscle fractional O2 extraction capacity. Indeed, the impairment of muscle oxidative function was evident also during KE, when cardiovascular constraints to oxidative metabolism were reduced. References Harrison J (2013) Med Clin North Am 97:425–438 Kuo et al (2000) Am J Pathol 156:797–805 Parker Jr et al (1994) Neurology 44:1086–1090 Shea et al (2012) Curr Top Med Chem 12:2596–2610