Alzheimer’s is a form of dementia named after Dr. Alois Alzheimer, who first reported its symptoms in 1906. While examining the brain of one of his deceased mental illness patients, he observed dramatic morphological changes in the tissue such as abnormal clumps and tangled bundles of fibers. These phenotypes are now considered to be distinct features of Alzheimer’s disease. Of note, this irreversible, progressive brain disorder, which causes memory, thinking, and behavioral problems, is the sixth leading cause of death worldwide. Furthermore, nearly 50 million people live with this disease and an estimated $1 trillion was spent on disease care in 2018. However, no cure currently exists for Alzheimer’s.
Most scientists have agreed that, while many proteins seem to be involved in the disease, two, namely β-amyloid and tau, are critical for disease progression. At critical levels in the brain tissue, β-amyloid aggregates into plaque, disrupting cell function, while tau forms neurofibrillary tangles, thus blocking neuronal transport systems. What remains to be explained is whether — and how — these proteins might interact with each other.
Early Alzheimer’s diagnosis has always been a struggle for medical practitioners. Compared to cardiovascular diseases and high blood pressure for example, where more than 80% of patients are aware of the disease before definitive diagnosis, fewer than 50% of Alzheimer’s patients are aware of having the disease when they are finally diagnosed. Importantly, despite the lack of a cure for Alzheimer’s at present, early detection can provide both more chances and more time for patients and doctors to delay the disease’s progression.
A wealth of research has gone into studying Alzheimer’s. Novel achievements and interesting breakthroughs happen all the time, giving hope to future patients to fight the disease.
#1. The “Big Bang” of Alzheimer’s disease
University of Texas Southwestern researchers may have discovered what they call the Alzheimer’s “Big Bang” relating to tau pathology, which refers to the earliest point of dementia. They reported that the protein tau will, in fact, expose its otherwise hidden inner core due to misfolding prior to protein aggregation. They believe this exposure triggers the aggregation of tau proteins into eventual large toxic tangles. This discovery has added more options to future diagnosis and treatment, as more research can be focused on the detection of this abnormal tau protein and on intervention before the aggregation process.
#2. Herpes virus may cause Alzheimer’s
Another recent discovery on the cause of Alzheimer’s comes from the University of Manchester. Researchers found that active herpes simplex virus type 1 (HSV1) in the brain may cause cumulative damage. HSV1 is best known for causing cold sores, but research from this group first showed the link between the virus and Alzheimer’s disease in the 1990s. Their most recent work has shown that HSV1 infection in cultured cells triggers β-amyloid and tau protein aggregation. Moreover, the accumulation of these two proteins is characteristic of Alzheimer’s. Hence, these findings may lead to new treatments for Alzheimer’s, as antiherpes antiviral drugs might reduce the levels of β-amyloid and tau aggregation caused by HSV1.
#3. Artificial intelligence (AI) could be used for Alzheimer’s diagnosis
Researchers from Stanford University have developed a deep learning program that could help to diagnose Alzheimer’s disease. A 3D convolutional neural network was trained on a dataset from the Alzheimer’s Disease Neuroimaging Initiative. This neural network learned how to interpret test results from MRI data samples, so as to then diagnose Alzheimer’s. The model reached 94% accuracy, an improvement over two previous deep learning models and in line with accuracy of manual examination of MRI images. This model also indicated that the hippocampus region is critical for Alzheimer’s diagnosis.
#4. Tau-PET scanning improves diagnosis
One difficulty in Alzheimer’s diagnosis is that other conditions are known to cause similar symptoms. Recently, Lund University researchers developed a new brain imaging method to resolve this issue. This PET-based method can show the s specific tau protein deposits which are unique to Alzheimer’s. They used a special tau marker to assist in the imaging, thus making tau deposits clearly visible in certain areas that are specific to Alzheimer’s. Currently, the common screening methods for Alzheimer’s are MRI and β-amyloid-PET. This new tau-PET method was shown to have 90%-95% sensitivity, much higher than the current MRI method, as well as lower rates of false-positive diagnosis than the β-amyloid-PET method.
#5. Guidance for using lumbar puncture
Researchers in the United States, Sweden, and Spain have developed new criteria for using lumbar puncture, also named spinal taps, to diagnose Alzheimer’s. A lumbar puncture is a routine procedure that entails the insertion of a needle into the spine to extract cerebrospinal fluid for medical analysis. Using this procedure, β-amyloid and tau protein levels can be monitored for early Alzheimer’s diagnosis. These new guidelines detailing when and how to use these tests were published to help medical professionals increase the accuracy of early diagnosis.
#6. Eye scanning can detect Alzheimer’s
Researchers at Duke University developed a cheap, fast, and easy eye scanning method for Alzheimer’s diagnosis. They found that Alzheimer’s patients have fewer small retinal blood vessels at the back of the eye and a thinner specific layer of the retina compared to healthy patients. This symptom can be easily detected by a quick, painless eye scan. If this method could be used in clinics, then the number of patients that could be screened would increase dramatically, which is critical for subsequent treatment.
#7. Alzheimer’s disease progression can be delayed by antidepressants
Antidepressants were found to have effects on Alzheimer’s by researchers from the University of Waterloo. One class of antidepressants, called selective serotonin reuptake inhibitors (SSRIs), have been shown to have an effect in delaying the development and growth of β-amyloid protein aggregates. Though this study is still at its early stages, it provides a promising future direction for the treatment of Alzheimer’s disease. Since the drugs have already been approved by the government, future research is sure to be in the pipeline.
#8. Exercise could protect the brain from Alzheimer’s
A recent study showed that exercise alone could slow down the spread of dementia by helping to clean the waste from damaged nerve cells in mice. Exercised animals were found to have enhanced memory, and for mice with Alzheimer’s, it can also help them recover brain function. Even though the difference between mice and humans remains a concern, these data are certainly inspiring, although more research should be done in this direction to understand the strength of the benefits and the optimal program.
#9. Memory loss could be reversed by blocking HDAC activity
Histone deacetylases (HDACs) are an important family of enzymes involved in regulation of gene expression by making DNA less accessible to transcription factors. MIT researchers have found that blocking the activity of one such enzyme, HDAC2, could reverse memory loss in mice. This is due to the enzyme’s responsibility in blocking memory-linked gene function. Interestingly, HDAC2 levels were shown to be elevated in Alzheimer’s disease patients. Typically however, HDAC inhibitors block all members of the HDAC family, leading to toxic side effects. Recently, the same research group from MIT found a method to specifically inhibit HDAC2 by blocking its interaction with a binding partner called Sp3, thus potentially avoiding the side effects. This finding opens possibilities to develop a new treatment for Alzheimer’s.
#10. First early stage Alzheimer’s patient treated using ultrasound
Recently, researchers from West Virginia University successfully performed the first procedure to treat an early-stage Alzheimer’s patient using focused ultrasound. They used the ultrasound waves to open the patient’s blood-brain barrier, which would otherwise block large molecules and medications from flowing into the brain. This technique had previously been successfully used for cleaning clusters of proteins associated with Alzheimer’s in animals. This success is definitely encouraging and could prove a treatment option for many patients with early signs of Alzheimer’s.
Much exciting recent research has been conducted on the causes, diagnosis, and treatment of Alzheimer’s disease. Some approaches are improving existing studies like PET studies, while others make use of innovative tools such as AI for diagnosis. None of these studies stand in isolation, as each contributes to a deeper understanding of the field that will enable future breakthroughs. The successes we have highlighted in this article are truly exciting, and they provide hope that we will one day soon fully understand Alzheimer’s disease and can arrive at a cure.
