APP mutations in the A beta coding region are associated with abundant cerebral deposition of A beta 38

作者：Moro Maria Luisa; Giaccone Giorgio^*; Lombardi Raffaella; Indaco Antonio; Uggetti Andrea; Morbin Michela; Saccucci Stefania; Di Fede Giuseppe; Catania Marcella; Walsh Dominic M; Demarchi Andrea; Rozemuller Annemieke; Bogdanovic Nenad; Bugiani Orso; Ghetti Bernardino; Tagliavini Fabrizio

来源：Acta Neuropathologica, 2012, 124(6): 809-821.

DOI：10.1007/s00401-012-1061-x

• A beta 38
• Alzheimer%26apos
• s disease
• Familial disease
• Amyloid
• Immunohistochemistry

A beta is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into oligomers, protofibrils and fibrils is considered a seminal event in the pathogenesis of AD. A beta with C-terminus at residue 42 is the most abundant species in parenchymal deposits, whereas A beta with C-terminus at residue 40 predominates in the amyloid of the walls of large vessels. A beta peptides with other C-termini have not yet been thoroughly investigated. We analysed A beta 38 in the brains of patients with A beta deposition linked to sporadic and familial AD, hereditary cerebral haemorrhage with amyloidosis, or Down syndrome. Immunohistochemistry, confocal microscopy, immunoelectron microscopy, immunoprecipitation and the electrophoresis separation of low molecular weight aggregates revealed that A beta 38 accumulates consistently in the brains of patients carrying APP mutations in the A beta coding region, but was not detected in the patients with APP mutations outside the A beta domain, in the patients with presenilin mutations or in subjects with Down syndrome. In the patients with sporadic AD, A beta 38 was absent in the senile plaques, but it was detected only in the vessel walls of a small subset of patients with severe cerebral amyloid angiopathy. Our results suggest that APP mutations in the A beta coding region favour A beta 38 accumulation in the brain and that the molecular mechanisms of A beta deposition in these patients may be different from those active in patients with familial AD associated with other genetic defects and sporadic AD.

• 出版日期2012-12
• 单位河北医科大学