1998 marked the bicentennial for the publication of Edward Jenner's first manuscript on successful immunization against smallpox – a manuscript that changed modern medicine forever and the course of human history. It is amazing to think that more than two hundred years had to pass until the potential of the concept of immunization would begin to be realized for non-infectious diseases. Alzheimer's disease (AD), the most widespread and one of the most devastating neurological disorders, remains without effective cure. The culprit of AD is β-amyloid (Aβ), a fibrillar 40–42 amino-acid peptide accumulating in the brains of AD patients and eliciting neuronal cell death. The past two years has witnessed a flood of papers, following the pioneering work of Dale Schenk and his colleagues from Elan Pharmaceuticals (Dublin, Ireland), and addressing the potential of immunization with Aβ itself for slowing amyloid deposition in animal AD models. The logic behind this scheme is that immunization will stimulate the immune system to fight the abnormal pathologies associated with Aβ and thereby accelerate removal of the amyloid plaques. However, concern has been raised that immunization of AD patients with Aβ might initially accelerate the brain's amyloid deposition process, as the peptide crosses the blood–brain barrier and could seed further fibril formation and further neuronal death. Even without this extra risk, the notion of immunization with a toxic peptide does not sound very attractive.A new study by Sigurdsson et al. 1xImmunization with a nontoxic/nonfibrillar amyloid-β homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. Sigurdsson, E.M. et al. Am. J. Pathol. 2001; 159: 1–9Abstract | Full Text | Full Text PDFSee all References1 presents new hopes that this concern will soon be resolved. The study employed immunization with an alternative peptide K6Aβ1-30-NH2 that is similar to Aβ, highly soluble in water (unlike natural Aβ), includes the immunogenic Aβ1–11 and Aβ22–28 regions yet is entirely nontoxic and nonfibrillar. Repeated immunization with this Aβ-like peptide reduced amyloid deposition in brains of transgenic Tg2576 APP mice–animals frequently used as an AD model because of their similar brain pathology. After 7 months from the beginning of the protocol, the immunized mice demonstrated a reduced burden of Aβ plaques in both the cortical and hippocampal regions of the brain.It remains to be seen whether this immunization method will also diminish the AD-like memory impairment observed in similar AD animal models. Hopefully, this new approach will open the door for safer human trials in AD patients. Jenner's legacy seems to have been awakened and is thriving – this could trumpet the dawn of a new exciting chapter in modern medicine, where non-infectious diseases, possibly including stroke and nerve trauma 2xProtective autoimmunity: regulation and prospects for vaccination after brain and spinal cord injuries. Schwartz, M. and Kipnis, J. Trends Mol. Med. 2001; 7: 252–258Abstract | Full Text | Full Text PDF | PubMed | Scopus (118)See all References2, will become treatable by vaccination.