Short Amyloid-β (Aβ) Immunogens Reduce Cerebral Aβ Load and Learning Deficits in an Alzheimer's Disease Mouse Model in the Absence of an Aβ-Specific Cellular Immune Response

Abstract

Amyloid-␤ (A␤) immunotherapy lowers cerebral A␤ and improves cognition in mouse models of Alzheimer's disease (AD).

Suppressed Accumulation of Cerebral Amyloid β Peptides in Aged Transgenic Alzheimer’s Disease Mice by Transplantation with Wild-Type or Prostaglandin E2 Receptor Subtype 2-Null Bone Marrow

“…For example, A␤ vaccine protocols also reduce mouse hippocampal and cerebral A␤ plaque burden by about 50%, and this is associated with significant improvement in Morris water maze performance. 33,34 Because we observed similar reductions in cerebral A␤ plaque burden in these studies, we anticipate improved performance on future behavioral tests and neuropathological correlates of behavior. However, interpretation of these results may be challenging.…”

Vaccination with Aβ-Displaying Virus-Like Particles Reduces Soluble and Insoluble Cerebral Aβ and Lowers Plaque Burden in APP Transgenic Mice

“…These strategies included A␤ epitope presentation in tandem and/or branched structures either alone or in conjunction with known strong Th cell epitopes (31,45,46,49,52). In some approaches, immunogenicity was further enhanced by coadministration of strong adjuvants (45,46). However, adjuvants that potently stimulate innate immune responses may have unwanted effects in humans-even if considered safe in mouse models (10 -12, 14, 53).…”

Increased T Cell Recruitment to the CNS after Amyloid β1–42Immunization in Alzheimer's Mice Overproducing Transforming Growth Factor-β1

“…Passive immunization, in which a recombinant anti-A␤ antibody is directly injected and the host T cell response is bypassed, has shown efficacy in several mouse models (Bard et al, 2000;Schenk, 2002;Levites et al, 2006), and this approach is currently in phase 2 clinical trials (Bapineuzumab). New techniques that modulate the immune response to A␤ are being developed (Kim et al, 2005;Maier et al, 2006). Peripheral blood from patients in the AN1792 immunization trial demonstrated increases in mul- tiple pro-inflammatory genes in those who would go on to develop symptoms after immunization, implying that peripheral immune status influenced the possibility of development of meningoencephalitis after treatment with AN1792 (O'Toole et al, 2005).…”