Intraneuronal advanced glycation endproducts in presenilin-1 Alzheimer??s disease
Authors:
- Claire E ShepherdCSClaire E Shepherd
- Heather McCannHMHeather McCann
- William S BrooksWBWilliam S Brooks
- John B J KwokJohn B J Kwok
- Thomas ArendtTAThomas Arendt
- Marianne HalluppMHMarianne Hallupp
- Peter R SchofieldPSPeter R Schofield
- Ralph N MartinsRMRalph N Martins
- Glenda M HallidayGHGlenda M Halliday
- 1 April 2002
- journal article
- research article
- Published by Wolters Kluwer Health in NeuroReport
- Vol. 13 (5) , 601-604
Abstract
The most frequently mutated gene resulting in dominantly inherited Alzheimer's disease is presenilin-1. We have used antibodies against advanced glycation endproducts (AGE) in brain tissue sections of four patients with three different presenilin I mutations. Accumulation of intracellular AGE was observed in 75-95% of pyramidal neurons in patients with presenilin-1 mutations, far exceeding the percentage of presenilin-1-, tau- or ubiquitin-positive neurons. This high level of AGE-modified proteins in vulnerable neurons is most likely explained by higher levels of their precursors (reactive (di)carbonyl products) or a slower turnover of the participating proteins. These conditions of carbonyl stress may contribute to increased neuronal dysfunction and vulnerability leading to the early disease onset.Keywords
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