Advanced Glycation End Products in Alzheimer's Disease and Other Neurodegenerative Diseases

Am J Pathol. 1998 Oct;153(4):1149-55. doi: 10.1016/S0002-9440(10)65659-3.

Abstract

Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but A beta negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Apolipoproteins E / metabolism
  • Cerebral Amyloid Angiopathy / metabolism
  • Cerebral Amyloid Angiopathy / pathology
  • Dementia / metabolism
  • Dementia / pathology
  • Female
  • Glycation End Products, Advanced / metabolism*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / metabolism
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Supranuclear Palsy, Progressive / metabolism
  • Supranuclear Palsy, Progressive / pathology
  • Syndrome
  • Temporal Lobe / blood supply
  • Temporal Lobe / metabolism
  • Temporal Lobe / pathology
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Glycation End Products, Advanced
  • tau Proteins