Cerebral Amyloid Angiopathy-Related Microbleeds and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease

J Alzheimers Dis. 2017;55(3):905-913. doi: 10.3233/JAD-160651.

Abstract

Background: Alzheimer's disease (AD) commonly accompanies cerebral amyloid angiopathy (CAA).

Objective: We aimed to reveal associations between CAA-related brain microbleeds and cerebrospinal fluid (CSF) markers in AD patients.

Methods: Patients with probable AD (n = 88) from consecutive patients in our memory clinic were evaluated for patient demographics, vascular risk factors, neuropsychological tests, apolipoprotein E phenotype, MRI including T2*-weighted image and fluid attenuated inversion recovery sequence, and CSF amyloid and tau markers.

Results: The 88 patients with AD included 15 with microbleeds only in cortical/subcortical regions (cortical microbleeds) that could be CAA-related, 16 with microbleeds only in deep locations (deep microbleeds), 3 with microbleeds in both cortical and deep locations (mixed microbleeds), and 54 without microbleeds. The CSF levels of amyloid β-protein 1-40 (Aβ40) and amyloid β-protein 1-42 (Aβ42) were significantly lower in patients with cortical microbleeds than in those without microbleeds (p = 0.001 and p = 0.027, respectively). The result remained unchanged after adjustment for age, sex, apolipoprotein E E4 presence, and leukoaraiosis.

Conclusions: CAA-related cortical microbleeds would be associated with lower CSF levels of Aβ40 and Aβ42 in AD, reflecting the deposition of both Aβ40 and Aβ42 in the cerebrovasculature.

Keywords: Alzheimer’s disease; biomarkers; cerebral amyloid angiopathy; cerebrospinal fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoproteins E / genetics
  • Cerebral Amyloid Angiopathy / cerebrospinal fluid*
  • Cerebral Amyloid Angiopathy / complications*
  • Cerebral Amyloid Angiopathy / diagnostic imaging
  • Cerebral Amyloid Angiopathy / genetics
  • Female
  • Humans
  • Intracranial Hemorrhages / cerebrospinal fluid*
  • Intracranial Hemorrhages / complications*
  • Intracranial Hemorrhages / diagnostic imaging
  • Leukoaraiosis / diagnostic imaging
  • Leukoaraiosis / etiology
  • Magnetic Resonance Imaging
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • Retrospective Studies
  • Risk Factors

Substances

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