SAGE KE Bulletin Board
Comment on Saito et al. Nat Med 11: 434-439
5 May 2005
Dietmar R. Thal
Comment on Saito et al. Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation. Nat Med 11: 434-439
Alzheimer's disease (AD) is associated with an increase of the soluble amyloid beta-peptide (Abeta)-levels in the brain as well as with the deposition of Abeta. For sporadic AD, it is suggested that the alteration of clearance mechanisms for Abeta plays an important role for the increase of soluble forms of Abeta and its deposition. The article of Saito et al. demonstrates that an age related downregulation of somatostatin expression is responsible for the downregulation of the neprilysin-related clearance of Abeta. This report indicates that the regulation of clearance pathways potentially leads to the development of sporadic late-onset AD. Moreover, regulation of Abeta clearance mechanisms becomes of pharmacological interest for the treatment of late-onset AD. In the light of the finding of Saito et al. (1) it is important to note that alterations of other clearance mechanisms such as an apolipoprotein E -dependent atroglial uptake of Abeta (2), microglial Abeta uptake following immunization (3) or the clearance along the perivascular spaces (4) may also contribute significantly to the increase of soluble Abeta levels and the deposition of Abeta. Morphological correlates for astroglial Abeta uptake (5-7) as well as for the alteration of the vessel wall of cerebral small vessels in AD (4, 8-11) are well known pathological features of sporadic late-onset AD. To sufficiently reduce the Abeta-load a simultaneous improvement of all altered physiological clearance pathways may be required for the treatment of sporadic AD.
1. Saito T, Iwata N, Tsubuki S, et al. (2005) Somatostatin regulates
brain amyloid beta peptide Abeta(42) through modulation of proteolytic
degradation. Nat Med 11: 434-439.
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