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

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 (A beta 42) and 1-40 (A(340) in cerebrospinal fluid (CSF) and plasma, and blood-brain barrier (BBB) function using albumin ratios. CSF A beta 42 was lowest in AD with MBs, whereas A beta 40 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 A beta 42, while a non-cerebral amyloid angiopathy specific MB distribution related to higher plasma A beta 40. 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 A beta 42 is retained in cerebrovasculature of AD patients with MBs, while in contrast. VaD patients may possibly drain amyloid. (C) 2012 Elsevier Inc. All rights reserved.