Could a vaccine prevent Alzheimer’s?

Aging


Alzheimer’s disease is a degenerative disease of the brain. Alzheimer’s affects the brain’s synapses, which are where information flows from neuron to neuron (1). As it progresses, protein fragments, called beta amyloid, build up outside the neurons (1). Another protein, tau, builds up inside the neurons creating what is known as a tau tangle (1). The buildup of these proteins interferes with the transfer of information between the neurons, leading to cognitive decline and dementia.

Besides the protein build ups, patients with AD also suffer from inflammation and shrinkage (atrophy) (1). Alzheimer’s brains are not able to metabolize glucose, the main fuel of the brain, as well as those without AD (1).

The outward signs of Alzheimer’s disease are memory loss, apathy, impaired communication, behavioral changes, and difficulty speaking, swallowing, and walking (1).

The effects of Alzheimer’s are not limited to the individual. Because of the slow degenerative process of the disease, the impact of Alzheimer’s disease is much higher than that of other diseases. On average, Alzheimer’s patient’s spouses spend an average of $12,000 per year providing care (2). Caregivers and families also suffer harm to their emotional and physical well-being. Caregivers find their role to be physically and emotionally stressful (2). 

Risk factors for Alzheimer’s disease include age, genetics, and family history (2). Other risk factors include cardiovascular disease, education level, social engagement, and traumatic brain injury (2). Research suggests that physical activity and a healthy diet may help decrease the risk for developing Alzheimer’s disease (3).

While there is no cure for Alzheimer’s disease, researchers have developed Alzheimer’s drugs. Most research has been aimed at removing the beta amyloid protein build up. This has been performed by giving patients beta amyloid antigens (active vaccination) or anti-beta amyloid antibodies (passive vaccination) (4). Unfortunately, the first active vaccine developed led to meningoencephalitis, inflammation of the brain and the membranes covering it (5).

Researchers at the University of Leicester, the University Medical Center Göttingen and the medical research charity LifeArc have approached the problem from a different angle. Instead of targeting the beta amyloid protein build up, they studied a soluble, possibly toxic, form of the beta amyloid protein (6). Their results were published in the journal, Molecular Psychiatry.

The research team discovered an antibody in mice which neutralized the shortened form of the beta amyloid protein (6). When mice with Alzheimer’s were given the antibody, TAP01, neuron death was prevented (6). Immunized mice also showed improved cognitive ability (6).

The research team then developed a version of TAP01 suitable for use in humans, called TAP01_04. They were able to determine the structure of the beta amyloid protein when the TAP01_04 antibody was attached to it. 

These antibodies target the early beta amyloid proteins which are found in the brains of Alzheimer’s patients (6). These antibodies are also less likely to have any of the negative side effects of the other Alzheimer’s disease vaccines.

The research team hopes to perform a clinical trial of the vaccine in humans in the future.

Resources:

  1. Alzheimer’s Association. 2020 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia. 2020;16(3):391-460. doi:10.1002/alz.12068
  2. Grabher BJ. Effects of Alzheimer Disease on Patients and Their Family. Journal of Nuclear Medicine Technology. 2018;46(4):335-340. doi:10.2967/jnmt.118.218057
  3. Treatments and Research. Alzheimer’s Disease and Dementia. Published 2019. Accessed November 16, 2021. https://www.alz.org/help-support/i-have-alz/treatments-research‌
  4. Panza F, Frisardi V, Solfrizzi V, et al. Immunotherapy for Alzheimer’s disease: from anti-β-amyloid to tau-based immunization strategies. Immunotherapy. 2012;4(2):213-238. doi:10.2217/imt.11.170‌
  5. meningoencephalitis. The Free Dictionary. Accessed November 16, 2021. https://medical-dictionary.thefreedictionary.com/meningoencephalitis‌
  6. Bakrania P, Hall G, Bouter Y, et al. Discovery of a novel pseudo β-hairpin structure of N-truncated amyloid-β for use as a vaccine against Alzheimer’s disease. Molecular Psychiatry. Published online November 15, 2021. doi:10.1038/s41380-021-01385-7





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