Stable size distribution of amyloid plaques over the course of alzheimer disease

Alberto Serrano-Pozo, Matthew L. Mielke, Alona Muzitansky, Teresa Gómez-Isla, John H. Growdon, Brian J. Bacskai, Rebecca A. Betensky, Matthew P. Frosch, Bradley T. Hyman

Research output: Contribution to journalArticle

Abstract

Amyloid β plaques are a key pathologic feature of Alzheimer disease (AD), but whether plaque sizes increase or stabilize over the course of AD is unknown. We measured the size distribution of total immunoreactive (10D5-positive) and dense-core (Thioflavin S-positive) plaques in the temporal neocortex of a large group of subjects with AD and age-matched plaque-bearing subjects without dementia to test the hypothesis that amyloid plaques continue to grow along with the progression of the disease. The size of amyloid β (10D5)-positive plaques did not differ between groups, whereas dense-core plaques from the group with AD were slightly larger than those from the group without dementia (∼25%-30%, p = 0.01). Within the group with AD, dense-core plaque size did not independently correlate with duration of clinical disease (from 4 to 21 years, p = 0.68), whereas 10D5-positive plaque size correlated negatively with disease duration (p = 0.01). By contrast, an earlier age of symptom onset strongly predicted a larger postmortem plaque size; this effect was independent of disease duration and the presence of the APOE[Latin Small Letter Open E]4 allele (p = 0.0001). We conclude that plaques vary in size among patients, with larger size distributions correlating with an earlier age of onset, but plaques do not substantially increase in size over the clinical course of the disease.

Original languageEnglish (US)
Pages (from-to)694-701
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume71
Issue number8
DOIs
StatePublished - Aug 1 2012

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Keywords

  • APOE genotype
  • Alzheimer disease
  • Amyloid plaques
  • Dense-core plaques
  • Plaque growth
  • Plaque size

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Serrano-Pozo, A., Mielke, M. L., Muzitansky, A., Gómez-Isla, T., Growdon, J. H., Bacskai, B. J., Betensky, R. A., Frosch, M. P., & Hyman, B. T. (2012). Stable size distribution of amyloid plaques over the course of alzheimer disease. Journal of Neuropathology and Experimental Neurology, 71(8), 694-701. https://doi.org/10.1097/NEN.0b013e31825e77de