Concentrations of beta-amyloid precursor protein processing products in cerebrospinal fluid of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

Steinacker, P., Hendrich, C., Sperfeld, A.D., Jesse, S., Lehnert, S., Pabst, A., von Arnim, C.A., Mottaghy, F.M., Uttner, I., Tuman, H., Ludolph, A., Otto, M.
Journal   J Neural Transm.
Analytes Measured   Abeta 38 , Abeta 40 , Abeta 42 , APP
Matrix Tested   Cerebrospinal fluid (CSF)
Year   2009
Volume   116
Page Numbers   1169-78
Application   Alzheimers
Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders with heterogeneous clinical presentation but common neuropathological characteristics and pathophysiological substrates, which led to the view of ALS and FTLD representing two manifestations of a clinicopathological spectrum. For both diseases, changes in metabolism of beta-amyloid precursor protein (APP) are reported. In a pilot study, we analyzed cerebrospinal fluid from patients of the ALS-FTLD spectrum for APP processing products. ALS patients show elevated absolute levels of soluble APP and a shift towards the nonamyloidogenic APP processing pathway in contrast to patients with FTLD or ALS + FTLD. Changes in Abeta pattern could be described, allowing separation of patients with pure FTLD from ALS + FTLD. Combination of sAPP and Abeta values improves group differentiation. These findings may provide information on pathophysiological processes in the ALS-FTLD disease spectrum and could have impact in neurochemical diagnosis. We propose to expand this study to larger patient groups comprising followed up cases with known neuropathology.

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