title: Intraneuronal advanced glycation endproducts in presenilin-1 Alzheimer's disease.
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.
authors.affiliation: Neuroimmunological Cell Biology (IZKF), Leipzig, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
authors.forename: Claire E
authors.initials: CE
authors.lastname: Shepherd
authors.forename: Heather
authors.initials: H
authors.lastname: McCann
authors.forename: William S
authors.initials: WS
authors.lastname: Brooks
authors.forename: John B J
authors.initials: JB
authors.lastname: Kwok
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.forename: Marianne
authors.initials: M
authors.lastname: Hallupp
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1
chemical_list: D017127:Glycation End Products, Advanced; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1