Microbleeds relate to altered amyloid-β metabolism in Alzheimer's disease

Neurobiol Aging. 2012 May;33(5):1011.e1-9. doi: 10.1016/j.neurobiolaging.2011.10.026. Epub 2011 Nov 26.

Abstract

Cerebral microbleeds (MBs) may relate to amyloid in dementia. We selected 26 probable Alzheimer's disease (AD) patients with MBs, 26 age- and sex-matched AD patients without MBs, 11 vascular dementia (VaD) patients, and 22 patients with subjective complaints. We measured amyloid beta 1-42 (Aβ42) and 1-40 (Aβ40) in cerebrospinal fluid (CSF) and plasma, and blood-brain barrier (BBB) function using albumin ratios. CSF Aβ42 was lowest in AD with MBs, whereas Aβ40 was selectively decreased in VaD. In plasma, amyloid-beta was nonsignificantly elevated in VaD compared with controls. Higher albumin ratios in VaD suggested blood-brain barrier dysfunction. A MB pattern suggestive of cerebral amyloid angiopathy (CAA) related to lower CSF Aβ42, while a non-cerebral amyloid angiopathy specific MB distribution related to higher plasma Aβ40. Amyloid-beta is differentially implicated in AD with MBs and VaD. MB distribution related to different amyloid profiles, supporting distinct etiologies. Our results suggest that Aβ42 is retained in cerebrovasculature of AD patients with MBs, while in contrast, VaD patients may possibly drain amyloid.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / complications
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Blood-Brain Barrier / metabolism
  • Cerebral Amyloid Angiopathy / blood
  • Cerebral Amyloid Angiopathy / complications
  • Cerebral Amyloid Angiopathy / metabolism*
  • Cerebral Hemorrhage / blood
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / metabolism*
  • Dementia, Vascular / blood
  • Dementia, Vascular / complications
  • Dementia, Vascular / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptide Fragments / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)