The mTOR Pathway: A Common Link Between Alzheimer's Disease and Down Syndrome.

Down syndrome (DS) is a chromosomal condition that causes many systemic dysregulations, leading to several possible age-related diseases including Alzheimer's disease (AD). This may be due to the triplication of the Amyloid precursor protein (APP) gene or other alterations in mechanistic pathways, such as the mTOR pathway. Impairments to upstream regulators of mTOR, such as insulin, PI3K/AKT, AMPK, and amino acid signaling, have been linked to amyloid beta plaques (Aβ) and neurofibrillary tangles (NFT), the most common AD pathologies.

Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2: preliminary findings.

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24).

The Role of Tau Pathology in Alzheimer's Disease and Down Syndrome.

: Individuals with Down syndrome (DS) exhibit an almost complete penetrance of Alzheimer's disease (AD) pathology but are underrepresented in clinical trials for AD. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation of Tau (p-Tau), which may seed pathology to bystander cells and spread.

Down Syndrome Biobank Consortium: A perspective.

Individuals with Down syndrome (DS) have a partial or complete trisomy of chromosome 21, resulting in an increased risk for early-onset Alzheimer's disease (AD)-type dementia by early midlife. Despite ongoing clinical trials to treat late-onset AD, individuals with DS are often excluded. Furthermore, timely diagnosis or management is often not available.

A New Role for RNA G-quadruplexes in Aging and Alzheimer's Disease.

Introduction: As the world population ages, new molecular targets in aging and Alzheimer's Disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored.

Methods: In this study, we examined human hippocampal tissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD.

Recipient Reaction and Composition of Autologous Sural Nerve Tissue Grafts into the Human Brain.

Parkinson's disease (PD) is a severe neurological disease for which there is no effective treatment or cure, and therefore it remains an unmet need in medicine. We present data from four participants who received autologous transplantation of small pieces of sural nerve tissue into either the basal forebrain containing the nucleus basalis of Meynert (NBM) or the midbrain substantia nigra (SN). The grafts did not exhibit significant cell death or severe host-tissue reaction up to 55 months post-grafting and contained peripheral cells.

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms.

Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many as four out of five patients who sustained COVID-19 will show one or several neurological symptoms that can last months after the infection has run its course. Neurological symptoms are most common in people who are less than 60 years of age, while encephalopathy is more common in those over 60.

BDNF mediates improvement in cognitive performance after computerized cognitive training in healthy older adults.

Introduction: The often-cited mechanism linking brain-derived neurotrophic factor (BDNF) to cognitive health has received limited experimental study. There is evidence that cognitive training, physical exercise, and mindfulness meditation may improve cognition. Here, we investigated whether improvements in cognition after these three types of structured interventions are facilitated by increases in BDNF.

Aging in Down Syndrome: Latest Clinical Advances and Prospects.

Down syndrome (DS), or trisomy 21, is the most common genetic cause of intellectual disability [...

Aging with Down Syndrome-Where Are We Now and Where Are We Going?

Down syndrome (DS) is a form of accelerated aging, and people with DS are highly prone to aging-related conditions that include vascular and neurological disorders. Due to the overexpression of several genes on Chromosome 21, for example genes encoding amyloid precursor protein (), superoxide dismutase (), and some of the interferon receptors, those with DS exhibit significant accumulation of amyloid, phospho-tau, oxidative stress, neuronal loss, and neuroinflammation in the brain as they age. In this review, we will summarize the major strides in this research field that have been made in the last few decades, as well as discuss where we are now, and which research areas are considered essential for the field in the future.

Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain.

Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS contains p-Tau at an early age.

Biomarkers show value of studying dementia in Down syndrome.

More than 90% of people with Down syndrome develop Alzheimer disease but receive little or no treatment for their dementia. Novel biomarkers of ageing and dementia bring new hope to this medically vulnerable population and can also help researchers understand dementia in other populations.

Opportunities, barriers, and recommendations in down syndrome research.

Background: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community.

Distinctive alteration of presynaptic proteins in the outer molecular layer of the dentate gyrus in Alzheimer's disease.

Synaptic degeneration has been reported as one of the best pathological correlates of cognitive deficits in Alzheimer's disease. However, the location of these synaptic alterations within hippocampal sub-regions, the vulnerability of the presynaptic versus postsynaptic compartments, and the biological mechanisms for these impairments remain unknown. Here, we performed immunofluorescence labelling of different synaptic proteins in fixed and paraffin-embedded human hippocampal sections and report reduced levels of several presynaptic proteins of the neurotransmitter release machinery (complexin-1, syntaxin-1A, synaptotagmin-1 and synaptogyrin-1) in Alzheimer's disease cases.

A multiplex chemiluminescent immunoassay for serological profiling of COVID-19-positive symptomatic and asymptomatic patients.

The COVID-19 pandemic affects more than 81 million people worldwide with over 1.7 million deaths. As the population returns to work, it is critical to develop tests that reliably detect SARS-CoV-2-specific antibodies.

A Cohort Study of the Temporal Stability of ImPACT Scores Among NCAA Division I Collegiate Athletes: Clinical Implications of Test-Retest Reliability for Enhancing Student Athlete Safety.

Objective: In this study we examined the temporal stability of the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) within NCAA Division I athletes across various timepoints using an exhaustive series of statistical models.

Methods: Within a cohort design, 48 athletes completed repeated baseline ImPACT assessments at various timepoints. Intraclass correlation coefficients (ICC) were calculated using a two-way mixed effects model with absolute agreement.

Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers.

Concussion or mild traumatic brain injury (mTBI) in athletes can cause persistent symptoms, known as post-concussion syndrome (PCS), and repeated injuries may increase the long-term risk for an athlete to develop neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), and Alzheimer's disease (AD). The Center for Disease Control estimates that up to 3.8 million sport-related mTBI are reported each year in the United States.

Centre of pressure velocity shows impairments in NCAA Division I athletes six months post-concussion during standing balance.

Sport-related concussion return to play (RTP) decisions are largely based on the resolution of self-reported symptoms and neurocognitive function. Some evaluators also incorporate balance; however, an objective approach to balance that can detect effects beyond the acute condition is warranted. The purpose of this study is to examine linear measures of biomechanical balance up to 6 months post-concussion, and to present preliminary diagnostic thresholds useful for RTP.

Further understanding the connection between Alzheimer's disease and Down syndrome.

Improved medical care of individuals with Down syndrome (DS) has led to an increase in life expectancy to over the age of 60 years. In conjunction, there has been an increase in age-related co-occurring conditions including Alzheimer's disease (AD). Understanding the factors that underlie symptom and age of clinical presentation of dementia in people with DS may provide insights into the mechanisms of sporadic and DS-associated AD (DS-AD).

RvE1 treatment prevents memory loss and neuroinflammation in the Ts65Dn mouse model of Down syndrome.

Inflammation can be resolved by pro-homeostatic lipids called specialized pro-resolving mediators (SPMs) upon activation of their receptors. Dysfunctional inflammatory resolution is now considered as a driver of chronic neuroinflammation and Alzheimer's disease (AD) pathogenesis. We have previously shown that SPM levels were reduced and also that SPM-binding receptors were increased in patients with AD compared to age-matched controls.

Traumatic brain injury increases plasma astrocyte-derived exosome levels of neurotoxic complement proteins.

Possible involvement of complement (C) systems in the pathogenesis of traumatic brain injury (TBI) was investigated by quantifying Cproteins in plasma astrocyte-derived exosomes (ADEs) of subjects with sports-related TBI (sTBI) and TBI in military veterans (mtTBI) without cognitive impairment. All sTBI subjects (n = 24) had mild injuries, whereas eight of the mtTBI subjects had moderate, and 17 had mild injuries. Plasma levels of ADEs were decreased after acute sTBI and returned to normal within months.

Receptors for pro-resolving mediators are increased in Alzheimer's disease brain.

Neuroinflammation is a key element of AD pathology and conceivably a result of a disturbed resolution. Resolution of inflammation is an active process which is strictly orchestrated following the acute inflammatory response after removal of the inflammatory stimuli. Acute inflammation is actively terminated by specialized pro-resolving mediators (SPMs) thereby promoting healing and return to homeostasis.