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.
Münch
Gerald
G
Neuroimmunological Cell Biology (IZKF), Leipzig, Germany.
Shepherd
Claire E
CE
McCann
Heather
H
Brooks
William S
WS
Kwok
John B J
JB
Arendt
Thomas
T
Hallupp
Marianne
M
Schofield
Peter R
PR
Martins
Ralph N
RN
Halliday
Glenda M
GM
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
D017127:Glycation End Products, Advanced; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1