Accumulation of intracellular amyloid-β peptide (Aβ 1-40) in mucopolysaccharidosis brains

Stephen D. Ginsberg, James E. Galvin, Viginia M.Y. Lee, Lucy B. Rorke, Dennis W. Dickson, John H. Wolfe, Margaret Z. Jones, John Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


To evaluate whether in vivo accumulations of heparan sulfate caused by inborn errors in the metabolism of glycosaminoglycans lead to the formation of neurofibrillary tangles and/or senile plaques, as seen in Alzheimer disease (AD), we studied postmortem brains from 9 patients, ages 1 to 42 years, with mucopolysaccharidosis (MPS). The brains of patients with Hurler's syndrome (MPS I; n = 5) and Sanfilippo's syndrome (MPS III; n = 4) as well as from caprine MPS IIID and murine MPS VII models were evaluated by thioflavine-S staining and by immunohistochemistry using antibodies directed against heparan sulfate proteoglycans, hyperphosphorylated tau, amyloid-β peptide precursor proteins (APP), and amyloid-β peptides (Aβ [1-40], and Aβ [1-42]). A two-site sandwich enzyme-linked immunosorbent assay (ELISA) was also utilized to compare levels of total soluble and insoluble Aβ (1-40) and Aβ (1-42) obtained from temporal cortex of MPS patients. Although no neurofibrillary tangles, senile plaques, or tau-positive lesions were detected in any of the MPS brains studied here, antibodies directed against Aβ (1-40) intensely and diffusely stained the cytoplasm of cells throughout the brains of the MPS patients and the caprine MPS model. The ELISA assay also demonstrated a significant 3-fold increase in the level of soluble Aβ (1-40) in the MPS brains compared with normal control brains. Thus, at least some of the metabolic defects that lead to accumulations of glycosaminoglycans in MPS also are associated with an increase in immunoreactive Aβ (1:40) within the cytoplasmic compartment where they could contribute to the dysfunction and death of affected cells in these disorders, but not induce the formation of plaques and tangles. Models of MPS may enable mechanistic studies of the role Aβ and glycosaminoglycans play in the amyloidosis that is a neuropathological feature of AD.

Original languageEnglish (US)
Pages (from-to)815-824
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Issue number8
StatePublished - Aug 1999


  • Amyloid-β peptides
  • Glycosaminoglycans
  • Heparan sulfate proteoglycan
  • Neurofibrillary tangles
  • Senile plaques
  • Tau protein

ASJC Scopus subject areas

  • General Medicine


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