About Alzheimer’s Disease

Monoclonal antibody treatment for Alzheimer’s disease represents an innovative field of research that focuses on utilizing monoclonal antibodies to reduce or eradicate characteristics associated with the disease’s progression. These antibodies are referred to as “monoclonal” because they’re lab-engineered to replicate the structure of natural antibodies produced and managed within the body. Monoclonal antibodies target tau and amyloid proteins, substances that have been the main focus of research due to their role in plaque formation in the brain.

Examples of monoclonal antibody therapies for Alzheimer’s disease include solanezumab, donanemab, lecanemab, and aducanumab. These antibodies work by preventing beta-amyloid and tau from forming plaques in the brain and by eliminating previously formed plaques. They aid the body in clearing these plaques by binding to the proteins and destroying them. The introduction of monoclonal antibodies stimulates both the immune system and the related responses in the body to react to these proteins.

Monoclonal antibodies are typically administered as intravenous (IV) solutions injected into the patient’s veins, which is a treatment known as an infusion. Each monoclonal antibody medication has a specific frequency for infusion administration, such as every four weeks for aducanumab. Infusion duration can vary and also includes additional observation time to monitor potential adverse reactions to the medication. There are also monoclonal antibodies that can be self-administered subcutaneously in the upper thigh or abdomen, but since some patients with Alzheimer’s disease may struggle with self-injection, a family member or caregiver usually takes on this responsibility. 

While monoclonal antibodies’ use in Alzheimer’s treatment shows promise, clinical trials have yielded mixed outcomes. For instance, phase 3 trials for bapineuzumab, solanezumab, gantenerumab, and crenezumab were discontinued due to a lack of efficacy. Despite these mixed results, other ongoing trials and dedicated development of monoclonal antibody treatments for Alzheimer’s disease continue. The outcomes for treatments like aducanumab and lecanemab, which was recently granted traditional approval by the FDA,  serve as a hopeful reminder that monoclonal antibodies may eventually provide an effective cure for Alzheimer’s disease.

Sources

“Aducanumab Discontinued as an Alzheimer’s Treatment”. Alzheimer’s Association. Retrieved from https://www.alz.org/alzheimers-dementia/treatments/aducanumab 

“FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval”. U.S. Food and Drug Administration. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval 

“Understanding How Monoclonal Antibodies Work”. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK572118/ 

“Alzheimer’s Treatments: What’s on the Horizon?”. Mayo Clinic. Retrieved from https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-treatments/art-20047780 

Early-onset Alzheimer’s disease is a form of dementia that develops prior to age 65. It generally strikes those in their 40s or 50s, but it can happen to someone as early as their 30s. It is estimated that 325,000 people, or one in 20 people with Alzheimer’s disease, have early-onset Alzheimer’s disease. However, a comprehensive compilation of studies released by Alzforum indicates prevalence may be higher.

For most people with early-onset Alzheimer’s disease, symptoms closely mirror those of other forms of Alzheimer’s disease, experts at Johns Hopkins Medicine note. The disease also progresses through the same stages of dementia as it does in people diagnosed after age 65.

Like the majority of dementias, the cause of early-onset Alzheimer’s is unknown. According to a study published in Oncotarget in 2018, genetic mutations may be a cause. But those mutations are rare, found in only 1% of people diagnosed with the disease. Genetic testing is available to those with a family history of early-onset Alzheimer’s. But the presence of abnormal genes does not always lead to development of the disease.

Early-Onset Alzheimer’s Diagnosis

Early-onset Alzheimer’s is often misdiagnosed. There are no diagnostic tools available to confirm it, and since it is uncommon among middle-aged adults, physicians can easily overlook it as a possible cause for cognitive decline. If you are experiencing cognitive symptoms, your doctor will administer cognitive testing of memory and other mental skills. They may also prescribe blood tests, urine tests, and CT or MRI scans of the brain. You may be referred to a neuropsychologist for further evaluation. 

If you suspect you or a loved one has early-onset Alzheimer’s disease, the Alzheimer’s Association recommends patients or caregivers contact a local chapter to find someone who specializes in Alzheimer’s disease in their area. Proper diagnosis is crucial for you and your family. Since most people diagnosed with early onset Alzheimer’s have a professional career, family obligations, and may be caregivers themselves, planning is essential. Financial and legal decisions must be made, as well as strategizing future care as the disease progresses.

With that being said, disease progression varies. Life expectancy for those with early-onset Alzheimer’s is unknown. But a wide range of 8 to 20 years of life is projected, similar to those with Alzheimer’s disease that develops later in life. As there may be a stigma attached to a diagnosis at such a young age, seek out family, friends, and your local Alzheimer’s Association chapter for support.  Clinical trials are underway to better understand the genetic, biological and clinical processes involved in younger-onset Alzheimer’s, so experts can develop better treatments in the future. Learn more about The Longitudinal Early-Onset Alzheimer’s Disease Study to see if you or a loved one may qualify to participate.

Sources

“Estimates of Young-Onset Dementia Prevalence Just Doubled”. AlzForum. https://www.alzforum.org/news/research-news/estimates-young-onset-dementia-prevalence-just-doubled 

“Early-Onset Alzheimer’s Disease”. Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/alzheimers-disease/earlyonset-alzheimer-disease 

“The genes associated with early-onset Alzheimer’s disease”. National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC5871104/ 

“Get Involved with Your Local Chapter”. Alzheimer’s Association. https://www.alz.org/local_resources/find_your_local_chapter 

“LEADS Longitudinal Early-Onset Alzheimer’s Disease Study”. Alzheimer’s Association. https://www.alz.org/leads/overview.asp 

There is no sure way to prevent Alzheimer’s disease. However, taking steps to limit your risk of cardiovascular disease and diabetes may help lower your risk of Alzheimer’s disease as well. According to the Harvard School of Public Health, these lifestyle decisions can help ward off diabetes, lower blood pressure and improve heart health and, by extension, promote brain health. .

• Maintain a normal weight. Overweight individuals are seven times as likely to develop diabetes. If you are obese, your risk of diabetes is 20 to 40 times greater than someone who maintains a healthy weight. Obesity also increases the risk of heart disease and stroke.
• Exercise. Two large studies — the Nurses’ Health Study and Health Professionals Follow-up Study — indicate that walking briskly for 30 minutes a day reduces the risk of developing type 2 diabetes by 30%. The Black Women’s Health Study showed similar results from walking briskly for five hours per week. Additionally, according to the American Heart Association, regular aerobic exercise — at least 30 minutes of moderate-intensity physical activity five times per week — also improves cardiovascular health.
• Turn off the TV. Obviously, the more time you spend sitting in front of the TV, the less time you spend engaged in physical activity. This may be why research shows that for every two hours of TV a person watches, their risk of developing diabetes increases 20%, and their risk of cardiovascular disease increases by 15%. 
• Stop smoking. Smoking increases your risk of cognitive decline, but quitting appears to help restore brain function to the level of people who have never smoked. 
• Eat a healthier diet. In general, this means doing the following:
  • Eating more whole grains, fruits and vegetables
  • Swapping sugary drinks for water or unsweetened coffee or tea
  • Eating polyunsaturated fats, such as those found in vegetable oils, olive oil, nuts and seeds, and avoiding trans fats, which often lurk in margarine, baked goods and fast food. [Hint: anything that contains “partially hydrogenated vegetable oil” contains trans fat.]

• Eating “fatty fish” such as salmon, herring, sardines, mackerel, lake trout and albacore tuna. The omega-3 fatty acids in these fish will not decrease the risk of diabetes, but they can protect against heart disease.  

Additionally, the CDC recommends that older adults maintain social connections and stay mentally active to slow cognitive decline and decrease the risk of Alzheimer’s disease. Protecting your brain from trauma is important as well. Some steps that can decrease the risk of head injuries include the following: 

• Wear a helmet if you ride a bike or participate in contact sports
• Wear your seatbelt whenever you’re in an automobile
• Protect against falls: Wear sensible shoes and remove clutter, scatter rugs and other items that could cause you to slip and fall in your home. 

Finally, uncorrected hearing and/or vision loss are closely associated with dementia risk. According to the Alzheimer’s Society, people with age-related vision loss (for example, due to cataracts) were 50% more likely to develop dementia. However, those who had cataracts removed were 30% less likely to go on to develop dementia than those who did not. Diabetic retinopathy — vision loss caused by consistently elevated blood sugar — is also a recognized risk factor for developing dementia. 

 Similarly, even mild uncorrected hearing loss can double an individual’s risk of developing dementia, while severe uncorrected hearing loss can increase the risk by five times. The risk increases the longer hearing loss continues. 

In order to mitigate these risks, it is important to:

• Have your hearing and vision checked annually
• Wear hearing aids if they have been prescribed
• Wear glasses or contact lenses as needed
• Speak with your provider about surgery if you have developed cataracts
• If you are diabetic, keep blood sugar at recommended levels to lower the risk of diabetic retinopathy

Sources

“Simple Steps to Preventing Diabetes”. The Nutrition Source. https://nutritionsource.hsph.harvard.edu/disease-prevention/diabetes-prevention/preventing-diabetes-full-story/ 

“Impact of Smoking on Cognitive Decline in Early Old Age”. JAMA Psychiatry. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/1151016 

“Hearing loss and the risk of dementia”. Alzheimer’s Society. https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia/reduce-your-risk-of-dementia/hearing-loss 

“Vision loss and the risk of dementia”. Alzheimer’s Society. https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia/reduce-your-risk-of-dementia/vision-loss-and-risk 

“Diabetic retinopathy”. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/diabetic-retinopathy/symptoms-causes/syc-20371611 

Yes, genetics can influence the development of Alzheimer’s, and it is linked to the early onset of the disease. However, multiple genes influence whether someone develops Alzheimer’s disease, and these genetic instances account for less than 1% of cases. Risk genes and deterministic genes determine whether someone develops a disease, and although there are Alzheimer’s genes found in both categories, identified cases of Alzheimer’s associated with genetics are attributed to deterministic genes. Additionally, many people who develop Alzheimer’s lack any previous family history of the disease.

Sometimes, genetic mutations can cause early-onset Alzheimer’s, resulting in what is known as early-onset familial Alzheimer’s disease. Mutations in the PSEN1, PSEN2, and APP genes are common in these cases. Early onset may also occur in cases with genetic changes that have yet to be identified. It is important to note that although genetics can increase the likelihood of developing Alzheimer’s, environmental and lifestyle factors can also exacerbate this likelihood.

While there is a genetic component involved in the development of Alzheimer’s disease, it is one of many factors involved rather than being the sole cause of the disease. It is crucial to understand both the genetic and non-genetic factors contributing to Alzheimer’s to develop appropriate preventative measures, as well as potential treatments. Ultimately, ongoing research in these areas is necessary for great insight into how to manage and prevent the disease in the future. 

Sources 

“Alzheimer’s disease.” Medline Plus. Retrieved from https://medlineplus.gov/genetics/condition/alzheimers-disease/#causes 

“Alzheimer’s disease genetics fact sheet.” National Institute on Aging. Retrieved from  https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/alzheimers-disease-genetics-fact-sheet 

“What are the causes and risk factors of Alzheimer’s and other dementias?” Alzheimer’s Association. Retrieved from https://www.alz.org/alzheimers-dementia/what-is-alzheimers/causes-and-risk-factors

No one is certain why some people get Alzheimer’s disease. Research has identified certain common characteristics in the brains of people with the illness, but why these things happen is still unclear. However, doctors now know that certain factors increase the risk of getting Alzheimer’s disease. These include the following:

• Advancing age: Alzheimer’s disease is not a normal part of aging. However, as the Alzheimer’s Association explains, increasing age is the single biggest risk factor for developing the disease. The risk of getting Alzheimer’s disease doubles every five years after the age of 65. By the time a person reaches 85, the risk is nearly 50%. 

• Family history: Having a close relative who has or had Alzheimer’s disease is associated with an increased risk of developing the disease. The risk increases if more than one family member has Alzheimer’s disease. 

• Genetics: Scientists have identified a number of genes that have an impact on Alzheimer’s disease. Three of these genes, amyloid precursor protein (APP), presenilin-1 (PS-1) and presenilin-2 (PS-2), cause a rare, inherited form of Alzheimer’s disease that usually strikes people in their 40s and 50s. A fourth gene, apolipoprotein E-e4 (APOE-4), increases the risk of Alzheimer’s disease but doesn’t necessarily cause it. The risk is higher if a person carries two copies of the gene (inherited from both parents). 

• Cardiovascular disease: A history of cardiovascular disease increases the risk of both Alzheimer’s disease and vascular dementia, as well as the risk of stroke. 

• Type 2 diabetes: A great deal of research links type 2 diabetes and Alzheimer’s disease. Although the mechanism isn’t clear, people with type 2 diabetes have a 70% chance of developing Alzheimer’s disease later in life, according to Alzheimer’s.net. This may be related to increased levels of beta amyloid and tau protein in the brain, but may also be a function of obesity, high blood pressure and cardiovascular disease, all of which are common in people with type 2 diabetes/

Sources

“Earlier Diagnosis”. Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/research_progress/earlier-diagnosis#apoe 

“How Alzheimer’s Could Be Type 2 Diabetes”. Alzheimers.net. https://www.alzheimers.net/2015-10-14-how-alzheimers-could-be-type-2-diabetes