Clinical Manifestations of Cerebral Amyloid Angiopathy-Related Inflammation

Ann Neurol. 2004 Feb;55(2):250-6. doi: 10.1002/ana.10810.

Abstract

To explore the clinical effects of inflammation associated with vascular deposits of the amyloid beta peptide (A beta), we analyzed 42 consecutive patients with pathologically diagnosed cerebral amyloid angiopathy (CAA) for evidence of an inflammatory response. Inflammation with giant-cell reaction surrounding amyloid-laden vessels was identified in 7 of the 42 cases. The clinical symptoms in each of the seven were subacute cognitive decline or seizure rather than hemorrhagic stroke, the primary clinical presentation in 33 of 35 patients with noninflammatory CAA (p < 0.001). Inflammatory CAA also was associated with radiographic white matter abnormalities, significantly younger age at presentation, and a marked overrepresentation of the apolipoprotein E epsilon 4/epsilon 4 genotype (71% vs 4%, p < 0.001). Of the six inflammatory CAA patients with available follow-up information, five demonstrated clinical and radiographic improvement after immunosuppressive treatment. The syndrome of CAA-related perivascular inflammation appears to represent a subset of CAA with clinically distinct symptoms that may respond to immunosuppressive treatment. These data add to evidence that inflammation against A beta can cause vascular dysfunction, a potential mechanism for the toxic response recently observed in clinical trials of A beta immunization.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Age Factors
  • Aged
  • Amyloid beta-Peptides / metabolism
  • Apolipoproteins E / genetics
  • Brain / blood supply*
  • Brain / pathology*
  • Cerebral Amyloid Angiopathy / complications
  • Cerebral Amyloid Angiopathy / drug therapy
  • Cerebral Amyloid Angiopathy / pathology*
  • Cerebral Amyloid Angiopathy / physiopathology*
  • Cerebral Hemorrhage / etiology
  • Cognition Disorders / etiology
  • Cyclophosphamide / therapeutic use
  • Female
  • Genotype
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / therapeutic use
  • Inflammation*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Risk Factors
  • Seizures / etiology
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Immunosuppressive Agents
  • Cyclophosphamide