Intraneuronal advanced glycation endproducts in presenilin-1 Alzheimer's disease
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.
|Authors||Munch, G.;Shepherd, C. E.;McCann, H.;Brooks, W. S.;Kwok, J. B.;Arendt, T.;Hallupp, M.;Schofield, P. R.;Martins, R. N.;Halliday, G. M. :|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11973454|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/1594|