An antigen-presenting dendritic vaccine with a specific antibody response could help Alzheimer's disease.

One of the two hallmark pathologies of Alzheimer's disease is hardened deposits of Aβ that clump together between nerve cells (amyloid protein plaques) in the brain; the other is neurofibrillary tangles of tau protein inside brain cells. Both lead to damaged neurological cell signaling, ultimately causing the onset of Alzheimer's disease and symptoms.

"This therapeutic vaccine uses the body's own immune cells to target the toxic Aβ molecules that accumulate harmfully in the brain, it provides strong immunomodulatory effects without inducing an unwanted, vaccine-associated autoimmune reaction in the aging mice."

Unfortunately, clinical trials of all anti-amyloid treatments for Alzheimer's disease so far have failed including the initial vaccine trial targeting Aβ (AN-1792), which was suspended in 2002 after several immunized patients developed central nervous system inflammation. Inflammation is a primary symptom of Alzheimer's disease, so any possible treatment with neural inflammation as a side effect essentially pours gas on the fire.

A next-generation anti-amyloid vaccine for Alzheimer's would ideally produce long-lasting, moderate antibody levels needed to prevent Aβ oligomers from further aggregating into destructive Alzheimer's plaques, without over-stimulating the immune systems of elderly people.

In this study, the researchers tested the vaccine they formulated using modified Aβ-sensitized dendritic cells derived from mouse bone marrow. Dendritic cells interact with other immune cells (T-cells and B-cells) to help regulate immunity, including suppressing harmful responses against healthy tissues.

"Because we use dendritic cells to generate antibodies, this vaccine can coordinate both innate and acquired immunity to potentially overcome age-related impairments of the immune system," Dr. Cao said.

The study included three groups of transgenic (APP/PS1) mice genetically engineered to develop high levels of Aβ and behavioral/cognitive abnormalities that mimic human Alzheimer's disease. One group was vaccinated with the investigational E22W42 DC vaccine, another received an endogenous amyloid beta peptide to stimulate dendritic cells (wild-type vaccine group), and the third was injected with dendritic cells only, containing no Aβ peptide (DC control group). A fourth group was comprised of untreated healthy, older mice (nontransgenic control group).

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Immunogenetics: open access