Intraneuronal advanced glycation endproducts in presenilin-I Alzheimer's disease

Gerald Münch; Claire E. Shepherd; Heather McCann; William S. Brooks; John B.J. Kwok; Thomas Arendt; Marianne Hallupp; Peter R. Schofield; Ralph N. Martins; Glenda M. Halliday

Intraneuronal advanced glycation endproducts in presenilin-I Alzheimer's disease

Gerald Münch, Claire E. Shepherd, Heather McCann, William S. Brooks, John B.J. Kwok, Thomas Arendt, Marianne Hallupp, Peter R. Schofield, Ralph N. Martins, Glenda M. Halliday^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

The most frequently mutated gene resulting in dominantly inherited Alzheimer's disease is presenilin-I. 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-I mutations, far exceeding the percentage of presenilin-I-, 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.

Original language	English
Pages (from-to)	601-604
Number of pages	4
Journal	NeuroReport
Volume	13
Issue number	5
Publication status	Published - 16 Apr 2002
Externally published	Yes

Keywords

Advanced glycation endproducts
Alzheimer's disease
Presenilin
Pyramidal neurons

Cite this

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title = "Intraneuronal advanced glycation endproducts in presenilin-I Alzheimer's disease",

abstract = "The most frequently mutated gene resulting in dominantly inherited Alzheimer's disease is presenilin-I. 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-I mutations, far exceeding the percentage of presenilin-I-, 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.",

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AU - Münch, Gerald

AU - Shepherd, Claire E.

AU - McCann, Heather

AU - Brooks, William S.

AU - Kwok, John B.J.

AU - Arendt, Thomas

AU - Hallupp, Marianne

AU - Schofield, Peter R.

AU - Martins, Ralph N.

AU - Halliday, Glenda M.

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AB - The most frequently mutated gene resulting in dominantly inherited Alzheimer's disease is presenilin-I. 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-I mutations, far exceeding the percentage of presenilin-I-, 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.

KW - Advanced glycation endproducts

KW - Alzheimer's disease

KW - Presenilin

KW - Pyramidal neurons

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Intraneuronal advanced glycation endproducts in presenilin-I Alzheimer's disease

Abstract

Keywords

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