Deposition of beta-amyloid subtypes 40 and 42 differentiates dementia with Lewy bodies from Alzheimer disease

Arch Neurol. 1999 Sep;56(9):1111-8. doi: 10.1001/archneur.56.9.1111.


Background: Alterations in the metabolism of the amyloid precursor protein and the formation of beta-amyloid (Abeta) plaques are associated with neuronal death in Alzheimer disease (AD). The plaque subtype Abeta(x-42) occurs as an early event, with Abeta(x-40) plaques forming at a later stage. In dementia with Lewy bodies (DLB), an increase in the amount of cortical Abeta occurs without severe cortical neuronal losses.

Objective: To advance our understanding of the natural history of Abeta in neurodegenerative diseases.

Design: We evaluated the expression of Abeta(x-40) and Abeta(x-42) in DLB using monoclonal antibodies and immunohistochemical techniques in 5 brain regions. The data were compared with those elicited with normal aging and from patients with AD.

Setting and patients: A postmortem study involving 19 patients with DLB without concurrent neuritic degeneration, 10 patients with AD, and 17 aged persons without dementia for control subjects.

Results: The Abeta plaques were more numerous in patients with DLB than in controls in most brain regions, although the Abeta(x-42) plaque subtype was predominant in both conditions. Overall, Abeta(x-42) plaque density was similar in patients with DLB and those with AD, but Abeta(x-40) plaques were more numerous in persons with AD than in those with DLB. The ratio of Abeta(x-40) to Abeta(x-42) plaques was significantly reduced in persons with DLB compared with patients with AD.

Conclusions: The Abeta plaques were more numerous in patients with DLB than persons with normal aging, but the plaque subtypes were similar. The relative proportion of the 2 Abeta plaque subtypes in DLB is distinguishable from that in AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / analysis*
  • Antibodies, Monoclonal
  • Brain Chemistry
  • Case-Control Studies
  • Dementia / metabolism*
  • Dementia / pathology
  • Female
  • Frontal Lobe / chemistry
  • Humans
  • Immunohistochemistry
  • Lewy Bodies / chemistry*
  • Male
  • Middle Aged


  • Amyloid beta-Peptides
  • Antibodies, Monoclonal