Sigurdsson EM, Scholtzova H, Mehta PD, Frangione B, Wisniewski T. Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. Am J Pathol. 2001 Aug;159(2):439-47. PubMed Abstract, View on AlzSWAN

REAGENTS/MATERIAL:

The peptides used (Ab1-40, Ab 1-42, Ab1-30-NH2, and K6Ab1-30-NH2) were synthesized at the Keck Foundation (Yale University, New Haven, CT), The peptide used for the immunizations, K6Ab1-30-NH2, maintains the two major immunogenic sites of Abpeptides, which are residues 1 to 11 and 22 to 28 of Ab 1-42 based on the antigenic index of Jameson and Wolf, and on preliminary results obtained in our laboratory.

Immunostaining on mouse brains used 6E10, 1:1000 (gift of Richard Kascsak, Institute for Basic Research), Anti-interleukin-1b,1:250 (Endogen, Rockford, IL), anti-OX-42, 1:250 (Biosource Int.), anti-GFAP, 1:500 (DAKO). For double-labeling of IL-1b and Amyloidb plaques, sections were first stained for IL-1b, (DAB/Ni; black) in which peroxidase was the enzyme. Sandwich ELISA was performed with anti-Ab R162 specific for Ab 40 and anti-Ab R165 specific for Ab 42.

FUTURE DIRECTION:
This group is currently further exploring the therapeutic potential of K6Ab1-30-NH2 and related peptides by using aluminum-based adjuvants that are approved for use in humans, and by assessing the behavioral status of the mice before and during the treatment period. Overall, the approach has a much lower risk of leading to toxic effects in humans, than the use of Ab1-40/42, while maintaining the therapeutic potential of immunization for AD.