Breakthroughs in Alzheimer Treatment Needed

Alzheimer disease has tremendous social and economic impact for which there is no known cure, however, strides in diagnosis and epidemiology could one day lead to breakthroughs in treatment. 

As one of the most common types of dementia, Alzheimer disease affects the parts of the brain that control thought, memory, and language. Disease progression typically begins with mild memory loss, with increasingly cognitive decline that can eventually lead to the loss of the ability to carry on conversations or respond to the environment.¹

According to the Centers for Disease Control and Prevention (CDC), as many as 5 million Americans were living with Alzheimer disease in 2014. The number of adults living with the disease doubles every 5 years after the age of 65. The CDC projects that 14 million people will be living with the disease by 2060.

Alzheimer is the sixth leading cause of death in the United States. On average, a person with Alzheimer's lives four to eight years after diagnosis, but can live as long as 20 years, depending on other factors.²

As the Alzheimer Association stated, this disease is not a normal part of aging. Scientists do not yet fully understand the underlying causes of Alzheimer disease but are vigilantly looking into a variety of common factors among patients.

Determining Risk Factors

The most significant risk factor for Alzheimer disease is age. Patients presenting with symptoms are usually later in life. Although, approximately 200,000 Americans under the age of 65 have been diagnosed with early-onset Alzheimer disease, further confirming that more research is needed to understand how the disease develops.²

Other common risk factors that could determine diagnosis are family history and genetics.

Scientists are finding more evidence that some of the risk factors for heart disease and stroke, such as high blood pressure and high cholesterol may also increase the risk of Alzheimer disease.¹ There is also growing evidence that physical, mental, and social activities could reduce these risk factors. 

Economic Burden

In 2010, the costs of treating Alzheimer’s disease were projected to fall between $159 and $215 billion.^1,3 By 2040, these costs are projected to jump to between $379 and more than $500 billion annually.^1,3

Death rates for Alzheimer’s disease are increasing, unlike heart disease and cancer death rates that are on the decline.^1,4 Dementia, including Alzheimer’s disease, has been shown to be under-reported in death certificates and therefore the proportion of older people who die from Alzheimer’s may be considerably higher.^1,5

Breakthroughs Beginning in the Brain

Much of what is known about the causes of Alzheimer disease comes from studying patients’ brains and developing new ways to understand the disease progression with different markers. Several studies exist to understand where exactly in the brain to pinpoint treatment and focus clinical trial efforts. 

Dallas P Veitch, Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA and the Northern California Institute for Research and Education, Department of Veterans Affairs Medical Center, San Francisco, CA, and colleagues created the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in an effort to validate biomarkers for Alzheimer disease clinical trials. 

“ADNI is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset Alzheimer disease,” stated the researchers in their study.⁶

The ADNI identifies 12 points to guide the development of novel biomarkers that could actually lower the costs of clinical trials, as well as duration, while remaining effective. Some results included:

• Data-driven AD progression models supported multifactorial interactions rather than a linear cascade of events.⁶
• β-Amyloid (Aβ) deposition occurred concurrently with functional connectivity changes within the default mode network in preclinical subjects and was followed by specific and progressive disconnection of functional and anatomical networks.⁶

A more recent study addresses the hallmark features of Alzheimer disease—the formation of neurofibrillary tangles (NFTs) and deleterious senile plaques that develop in the brain.

“Growing evidence implicates pathogens in Alzheimer disease development, with herpes simplex virus type I (HSV-1) gaining increasing attention as a potential causative agent,” explained Dana M, Cairns, PhD, Tufts University, and colleagues.⁷

Their study describes a multidisciplinary approach to produce physiologically relevant human tissues to study Alzheimer disease using human-induced neural stem cells (hiNSCs) and HSV-1 infection in a 3D bioengineered brain model. 

Their research resulted in a herpes-induced tissue model of Alzheimer disease that mimics human disease with multicellular amyloid plaque–like formations, gliosis, neuroinflammation, and decreased functionality, completely in the absence of any exogenous mediators of Alzheimer disease. This model will allow for future studies to identify potential downstream drug targets for treating this devastating disease.⁷

Future Initiatives 

Existing treatments only temporarily improve symptoms of the disease and potentially slow progression. Future Alzheimer's treatments may include a combination of medications, similar to how treatments for many cancers or HIV/AIDS include more than a single drug, according to the Mayo Clinic.⁸

For now, treatments strategies are being explored in a number of areas in an effort to combat the growing disease diagnosis rate. Most commonly, these treatments target microscopic clumps of the protein beta-amyloid (plaques). Addressing these begins with mimicking antibodies in the immune system to fight off the development of this plaque in the brain. 

Scientists are also researching how to keep the vital brain transport system called Tau to keep from tangling, which could reduce brain abnormalities. 

References:

1. What is Alzheimer's Disease? Centers for Disease Control and Prevention. https://www.cdc.gov/aging/aginginfo/alzheimers.htm. Published September 20, 2019. Accessed May 8, 2020.
2. What is Alzheimer’s? Alzheimer's Disease and Dementia. Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/what-is-alzheimers. Accessed May 8, 2020.
3. Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. NEJM. 2013;368(14):1326-34.
4. Tejada-Vera B. Mortality from Alzheimer’s disease in the United States: data for 2000 and 2010. NCHS data brief, no 116. Hyattsville, MD: National Center for Health Statistics. 2013.
5. James BD. Leurgans SE, Hebert LE, et al. Contribution of Alzheimer disease to mortality in the United States. Neurology. 2014;82:1-6.
6. Cairns DM, Rouleau N, Parker RN, Walsh KG, Gehrke L, Kaplan DL. A 3D human brain–like tissue model of herpes-induced Alzheimer’s disease. Science Advances. 2020;6(19). doi:10.1126/sciadv.aay8828.
7. Veitch DP, Weiner MW, Aisen PS, et al. Understanding disease progression and improving Alzheimer's disease clinical trials: Recent highlights from the Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement. 2019;15(1):106-152. doi:10.1016/j.jalz.2018.08.005
8. What new Alzheimer's treatments are on the horizon? Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-treatments/art-20047780. Published April 19, 2019. Accessed May 8, 2020.