Scientists have discovered inherited genetic mutations that are accountable for the development of autism. However, there is still no medication for treating ASD. A majority of the efforts have aimed to alleviate the symptoms and to help patients cope better with daily life. Experienced by 1 in 68 children, ASD has become the fastest growing and most commonly diagnosed developmental condition in Canada. This alarming fact presents a major challenge to scientists and clinicians alike. In response, pioneers in the ASD field have created the Transforming Autism Care Consortium (TACC).

The inauguration of TACC on Oct 23rd, 2017, helped to promote autism care in Quebec and advance autism research in general. The TACC network involves 44 member researchers from seven universities and five university hospital centers, and 227 member trainees from the community and overseas.

There seems to be a lack of communication amongst researchers, clinicians, and families in the process of seeking better care for autistic individuals. A researcher’s work on animal models might not apply to humans. Clinicians are unaware of novel treatments that ameliorate or reverse symptoms in animals. Behavioral treatments that yield positive outcomes in affected families are not effectively communicated to the other two groups. The lack of integration amongst the three main players leaves an enormous amount of available information squandered. Hence, the main purpose of TACC is to act as a communication hub for scientists and patients. Ultimately, TACC works toward bringing findings from basic research to clinical trials and from there to hospitals and families, and back.

The clinical scientists

The two-day conference has seen the participation of leaders in autism research not only from Canada, but also the United Kingdom, the United States, and France. Dr. Andrew Pickles, Director of King’s Clinical Unit at King’s College London, shared his approach to autism care with the Preschool Autism Communication Therapy. The program trains parents to better anticipate and cope with autistic children’s behaviors. Dr. David H. Skuse from University College London presented the cost-effective and accurate Developmental and Well Being Assessment (DAWBA) to generate clinically relevant diagnoses.  

The geneticist

On the other hand, geneticists are also working industriously to identify the root causes of neurodevelopmental conditions. For autism, the origin lies within the genetic codes: the DNA. Dr. Stephen Scherer of University of Toronto emphasized the importance of genome-wide association studies to develop an ASD gene list, which is crucial for precision medicine. He noted that ASD individuals need to be categorized into groups based on their genetic mutations, thus allowing for customized clinical care. This idea was a recurrent theme of TACC and was also advocated by Dr. Thomas Bourgeron from Institut Pasteur.

The basic researchers

The setbacks of most scientific conferences is that they involve either a majority of basic or clinical research. Basic research focuses on developing scientific theories, whereas clinical research focuses on applying these theories to practically solve problems. This creates an understanding gap that translational science needs to fill before developments can become beneficial to patients. TACC recognizes this problem and thus invited Dr. Nahum Sonenberg, a notable basic research scientist from McGill University, to be on its board of directors. At the conference, Dr. Sonenberg presented his recent finding: using metformin to reverse symptoms in mice that have Fragile X Syndrome, a genetic disease often co-diagnosed with autism. The talk gave clinicians more insights into how basic research is performed. Researchers and clinicians discussed the usefulness, the choice, and the translatability of animal models. They emphasized the importance of model organisms that harbour human mutations. This form of communication will undoubtedly facilitate the quality of basic research, which, in turn, will advance clinical research, and ultimately, healthcare.

The pioneers

When the word “pioneers” is mentioned in science, it often implies researchers and clinicians who have worked diligently to produce breakthroughs on a certain subject or disease. However, many forget that new treatments also require tremendous courage from families and patients, who were the pioneers to participate in novel clinical trials.

Understanding this significance, TACC is working towards establishing the Quebec 1000 (Q1K) family program. The program aims to create a comprehensive database with genetic, cellular, and behavioral information that is representative of the Quebec population. Researchers and clinicians can generate personalized profiles and decide which clinical trial will be most promising for each individual.

Collaboration is the key

It is becoming more apparent to scientists that advances cannot be achieved only by individual efforts. There has been increasing focus on multidisciplinary research and emphasis on collaboration. This idea was not missed during the TACC conference. Leaders in the field shared and allowed public access to databases such as MSSNG, Imagine ID, and mousetube. The conference also featured a networking activity, allowing young trainees to interact with each other and principal investigators from other universities within Quebec. This opportunity could potentially lead to new and exciting collaborations which might further autism research.

Bren Neale, a professor of University of Leeds once said, “Simply put, let the data be free.” And when the data is free, there will be people who will make good use of it. I agree with Dr. Laurent Mottron, one of the consortium’s scientific directors, who stated “the future of the autism field looks much brighter with the creation of TACC.” I am hopeful for the future of autism research and I look forward to attending future TACC conferences as we move forward in solving neurodevelopmental puzzles such as ASD.  

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Alzheimer’s disease (AD) is the most common cause of dementia. While the causes of AD have not been determined, its pathology is believed to be driven by the excessive accumulation of proteins that are found naturally in our body such as amyloid plaques and tau tangles. Outside the cells, amyloid bunches disrupt signaling between neurons and trigger inflammation, which can damage surrounding neurons. As opposed to amyloid plaques, tau tangles are found inside the cells. Modified tau proteins form neurofibrillary tangles, damaging neuronal cytoskeleton, and eventually lead to programmed cell death.

The majority of brain processes such as memory and learning depend on communications between neurons. In AD patients, neurons lose the capacity to relay information and decay over time. At early stages, complications such as wandering, getting lost, difficulty understanding questions, and slight behavioral and personality changes drastically affect quality of life. As the disease progresses, patients gradually have problems recognizing friends and family members, lose the ability to multi-task, and often experience hallucinations, delusions, and paranoia.

Current treatments aim at maintaining mental function, managing behavioral symptoms, and impeding the disease’s progression. While AD’s progression cannot be stopped or cured, early diagnosis allows patients and their families to seek professional help when the disease is at pre-clinical stage before the symptoms are evident. They can start coping and planning for the future by learning about the disease and developing support groups. In some cases, early intervention may potentially reverse some of the impairments. Unfortunately, most patients are not diagnosed until signs of cognitive deficits become apparent and irreversible. Furthermore, current diagnosis tests are often either invasive or expensive and time consuming. Due to the inconveniences, susceptible patients may be discouraged from taking the assessments. These problems call for a new diagnostic test that is less expensive, and minimally invasive, but that remains as accurate as the established ones.

Researchers from Lancaster University addressed these concerns in the recent edition of the journal Proceedings of the National Academy of Sciences of the United States of America. In this study, blood plasma from 549 individuals with various neurodegenerative diseases as well as age-matched healthy individuals were collected and analyzed with Fourier-transformed infrared spectroscopy (FTIR). FTIR is an analytical technique that measures the radiations absorbed by different chemical structures. It provides information about the unique molecular composition, and structures within each sample. “Interrogation of these samples with spectroscopic techniques allows for the generation of a spectral fingerprint, which subsequently facilitates the discrimination of the different populations and identification of potential biomarkers,” remarked Maria Paraskevaidi, the study’s lead author. Using classification algorithms, the researchers were able to differentiate between AD and healthy individuals with the accuracy reaching 86 per cent. This is as accurate as current diagnostic tests in the clinics but cost less money. In addition, differentiation of AD from other neurodegenerative diseases was achieved with satisfactory segregation and classification results. Notably, dementia caused by AD was distinguished from dementia linked to Lewy bodies (DLB), the second most common cause of dementia, with an accuracy of 90 per cent. Despite their similarities in symptoms, AD and DLB have been shown to respond distinctively to different medication. Correctly identifying AD and DLB can help a doctor devise appropriate clinical management, which will in turn improve the patient’s quality of life.  

This study introduces a new, convenient, and highly accurate test for diagnosing AD. Current tests involve the laborious process of collecting cerebrospinal fluid or the expensive and time-consuming brain imaging. Other blood-based techniques focusing on measuring levels of amyloid beta (Aβ) and tau proteins have yielded contentious results; the plasma level of Aβ was reported to increase in some studies and decrease in others. In fact, a recent meta-analysis of 231 studies has come to the conclusion that level of plasma Aβ is not strongly correlated with AD, and should not be used in clinical practice for diagnosis. Similarly, the level of plasma tau has been investigated as biomarker for AD. While the level of  plasma tau is increased in AD patients compared to healthy controls was a consensus view among researchers, the finding needs further verifications in larger cohorts. At the present, “there is no single definitive medical test for diagnosing AD,” said Paraskevaidi. However, with incredible efforts like the one in this study, we are getting closer to a test that would allow for early and accurate diagnosis of AD. I feel more hopeful as I reflect upon Alois Alzheimer’s saying “Excessive reservations and paralyzing despondency have not helped the sciences to advance nor are they helping them to advance, but a healthy optimism that cheerfully searches for new ways to understand, as it is convinced that it will be possible to find them.”

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In a newly published article in the journal Frontiers in Human Neurosciences, researchers from Beijing Jiaotong University employed data from Diffusion Tension Imaging (DTI) to investigate brain structures of 111 adults aged 18-55 years.  DTI is a specific type of MRI that measures the diffusion process of water molecules in particular and thus maps out the white matter in different brain regions. The DTI methods produce multiple outputs such as Fractional Anisotropy (FA), Axial and Radial Diffusion (AD & RD), and Mean Diffusion (MD). Fluctuations in these measurements can indicate  changes in various brain structures.

Tian and Ma observed an overall reduction in FA with age, including the period between early to mid-adulthood, which suggests that the integrity of the white matter is diminishing in regions such as the bilateral corticospinal tract (CST), the corpus callosum (CC), the fornix, the left superior longitudinal fasciculus (SLF), and the inferior longitudinal fasciculus (ILF). Additionally, significant age-related lessening of AD and increasing RD, implying axonal degeneration and demyelination respectively, were detected in the CC and the CST. Based on these findings, Tian and Ma were able to devise models to accurately predict an individual’s age based on any one of the DTI outputs. The accuracy of the age prediction models corroborates that microstructural changes in the brain between early to mid-adulthood  are in fact substantial.

Although it is unequivocal that there are significant changes in brain structures in the early and late stages of life, “the changes in brain structures and functions from early to mid-adulthood were largely unknown,” noted Tian. Based on the potentially mistaken assumption that brain structure is stable between early to mid-adulthood, many relevant studies might have neglected the age effect, which could  lead to flawed results. Tian and Ma’s findings alarmed scientists at the brain’s measurable microstructural changes over this previously untested developmental period. They also provided the possibility of valuable insight into how different structures are involved in cognitive decline and when that decline happens. The structures which were found to undergo the earliest changes, such as fornix, CC, and ILF, are crucial to memory, learning capacity, and reaction time. “When does cognitive decline begin?” is still a considerably contentious question in the field of brain development. Many researchers argue that cognitive decline surfaces as early as 20 years of age, while others claim that the impairment is not possible until after the age of 60. Tian and Ma’s results might even be useful for determining the emergence of senility, which could help design both preventative and interventional treatments for patients. In addition, Tian and Ma’s data suggests the previously mentioned structures to potentially play a role in cognition decline and the onset of the Alzheimer’s disease.

Despite the implications of this study in the field of brain development, the methods employed have several limitations. The results were obtained from a cross-sectional study, which examined people of varying ages. Cross-sectional studies only provide one measurement per subject. These studies are not ideal because they “could not rule out the possibility that the current results may, to some degree, be influenced by factors such as cohort effects, which are inevitable in studies based on cross-sectional data,” admitted Tian. McGill professor David Rudko shared his views with the Daily on the direction of future research. He noted that, “[Tian and Ma’s] results should be supplemented with future studies using longitudinal imaging.” The technology of DTI is still at its infant stage; hence, estimation errors are not negligible. Rudko suggested that the statistically significant correlations between age and microstructures should be further evaluated using more advanced microstructural techniques to ensure their validities.

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