Alzheimer’s disease is generally considered to have two key hallmarks: beta-amyloid and tau. These proteins form toxic clumps in the brains of Alzheimer’s patients and are believed to be the main drivers of the disease (see Alzheimer’s Disease: A general overview). In the past, the majority of attempts to develop a vaccine or cure for Alzheimer’s have focused on reducing levels of beta-amyloid. These trials have been largely unsuccessful; of more than 244 drug candidates tested in the past decade, only one has made it past clinical trials, a failure rate of more than 99% (see Where’s our cure to Alzheimer’s disease?) .
One reason for these failures may be that beta-amyloid begins accumulating long before the symptoms of Alzheimer’s develop, causing vaccines to be ineffective by the time they’re administered. In contrast, tau is believed to accumulate at a later stage than beta-amyloid . Some have proposed that beta-amyloid immunotherapy may be most effective when implemented in the earliest stages of Alzheimer’s, while drugs targeting tau could have therapeutic benefits during more advanced stages .
Another reason for the high failure rate of Alzheimer’s drug candidates is the prevalence of harmful side effects in clinical trials. In particular, a severe and possibly fatal condition called meningoencephalitis, which results in inflammation of the brain and meninges, has forced multiple trials to be ended prematurely. Though the direct cause is unknown, one possibility is that autoreactive T cells may be involved. Normally, vaccines work by triggering the creation of memory B cells. These cells produce protective antibodies against the harmful protein, leading to adaptive immunity. It’s believed that in addition to activating B cells, the failed Alzheimer’s vaccines can trigger another type of immune cell called autoreactive T cells, which can enter the brain and cause meningoencephalitis .
In a study published last week in Nature Scientific Reports, researchers created the first vaccine to target both beta-amyloid and tau . The researchers in this study combined a vaccine that had been previously shown to trigger a strong immune response to beta-amyloid with a newly-designed vaccine for tau. When the dual vaccine was administered to mice, along with an immune system enhancer called Advax, they developed high levels of antibodies against both beta-amyloid and tau. This suggests that the mice could be resistant to Alzheimer’s disease in the future.
The new treatment also addresses the common problem of meningoencephalitis. The two vaccines are designed using a new platform called MultiTEP, which allows them to specifically trigger a B cell immune response but not autoreactive T cells . The researchers hope that this may prevent the vaccine from causing autoimmune reactions.
Future studies are still needed to determine the effectiveness of this vaccine at preventing Alzheimer’s in humans. The authors of the study expect clinical trials to begin within the next 3-5 years .