Building on decades of research, a new paper brings us one step closer to a vaccine that targets the neurological hallmarks of Alzheimer's disease. Prevention may soon be possible.

Alzheimer's disease, the most common form of dementia, is a degenerative neurological disease.

Memory issues are often the first sign of the condition, which steadily progresses over time.

Alzheimer's disease is a growing concern as it appears almost exclusively in older adults. As the number of older people rises in the US, the number of cases will also increase.

Although scientists are still investigating the exact causes of Alzheimer's disease, they believe that certain neurological markers play a significant role.

The disease seems to involve a buildup of specific proteins in the brain called beta-amyloid and tau. Doctors refer to these abnormal congregations as plaques and neurofibrillary tangles respectively.

The hunt for a vaccine

Current treatments for Alzheimer's do not stop disease progression, so the search for effective alternatives is ongoing. Some researchers hope that targeting amyloid buildup might make it possible to stop Alzheimer's in its tracks.

Many scientists are on the hunt for a vaccine, including Dr. Roger Rosenberg, founding director of the Alzheimer's Disease Center at UT Southwestern in Dallas, TX.

Earlier studies demonstrated that introducing antibodies to amyloid proteins significantly reduces protein buildup. In the early 2000s, scientists used this knowledge to create a vaccine. However, when they tested the vaccine in humans, it caused inflammation in the brains of 6% of the participants, making it too dangerous to be usable.

Since then, scientists have focused on developing a way to produce antibodies that bind to Alzheimer's proteins without triggering the T-cell response that led to brain inflammation.

In Dr. Rosenberg's latest paper, he describes a new approach. His team started by injecting DNA coding for amyloid into the skin rather than the muscle. The injected cells created a three-molecule chain of beta-amyloid (ab42).

This molecule chain sparked an immune response, generating antibodies that target ab42. The antibodies prevented the buildup of amyloid plaques and also indirectly prevented the buildup of tau.

The current study examined this response in mice and found that the vaccine produced a 40% reduction in beta-amyloid and up to a 50% reduction in tau. Importantly, there were no adverse immune reactions.

"This study is the culmination of a decade of research that has repeatedly demonstrated that this vaccine can effectively and safely target in animal models what we think may cause Alzheimer's disease," says Dr. Rosenberg, who is excited about the results. "I believe we're getting close to testing this therapy in people."

The results recently featured in the journal Alzheimer's Research & Therapy.

Passive versus active immunization

A number of laboratories are using different approaches to develop a vaccine for Alzheimer's. For instance, some researchers are focused on using a passive immunization technique. They are developing vaccines against tau and amyloid proteins in the laboratory and then injecting them into people with Alzheimer's.

Dr. Rosenberg has taken a different approach by focusing on active immunotherapy, which involves triggering the body to produce antibodies. This method makes it easier to produce the vaccine and is more cost-effective than passive immunization. Also, triggering the body's immune response creates a wider range of antibodies, which may potentially be more effective.

As Alzheimer's generally appears later in life, relatively small delays in its development could make a substantial difference.

"If the onset of the disease could be delayed by even 5 years, that would be enormous for the patients and their families. The number of dementia cases could drop by half."

—Dr. Doris Lambracht-Washington, senior author

In the future, the researchers hope that tests will be available to detect plaques and tangles before symptoms appear. Theoretically, doctors could then provide the individual with an effective vaccine after identifying these early signs. This vaccine would prevent further protein buildup, thereby halting the progression of Alzheimer's.

As Dr. Rosenberg says, "The longer you wait, the less effect it will probably have. Once those plaques and tangles have formed, it may be too late."

There is still a long path to tread. First, researchers must trial the vaccine in humans, which will be a long process in itself. Alongside this process, scientists will hopefully continue to make progress in the early detection of Alzheimer's pathology.