Glycation and microglial reaction in lesions of Alzheimer's disease

Dennis W. Dickson, Stefano Sinicropi, Shu Hui Yen, Li Wen Ko, Linda A. Mattiace, Richard Bucala, Helen Vlassara

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Single, double, and triple immunostaining of cryostat sections of elderly normal and Alzheimer disease (AD) brain was performed with monoclonal and polyclonal antibodies to advanced glycation end products (AGE). The sections were counterstained with thioflavin-S or with immunocytochemistry for Aβ and also stained with markers for microglia. AGE-immunoreactivity was detected in senile plaques and neurofibrillary tangles (NFT). AGE immunoreactivity was most intense in dense or reticular amyloid deposits and extracellular NFT, while intracellular NFT and diffuse amyloid had less AGE immunoreactivity. This pattern of immunoreactivity was similar to that noted in previous studies with antibodies to apolipoprotein-E (apo-E). Therefore, double labeling with antibodies to apo-E and AGE was performed. AGE immunoreactivity colocalized to a very high degree with apo-E immunoreactivity, except that relatively more intense apo-E immunoreactivity was detected in amyloid deposits and more intense AGE immunoreactivity in NFT. The lesions that were immunostained with antibodies to AGE and apo-E were often, but not always, associated with a local microglial reaction. The results raise the possibility that apo-E or a fragment of apo-E may be glycated. Biochemical studies are needed to determine the extent of possible apo-E glycation in AD. The present results raise the possibility that glycation may serve as one of the signals for activation of microglia associated with amyloid deposits and extracellular NFT.

Original languageEnglish (US)
Pages (from-to)733-743
Number of pages11
JournalNeurobiology of aging
Issue number5
StatePublished - Jan 1 1996


  • AB
  • AGE
  • Apolipoprotein-E
  • Glycation
  • Immunocytochemistry
  • Immunofluorescence
  • Microglia
  • Neurofibrillary tangles
  • PHF-τ
  • Senile plaques

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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