Three stages to COVID-19 brain damage identified
The Journal of Alzheimer's Disease published a paper June 8, 2020, with a comprehensive review of COVID-19's effect on the nervous system. The authors warn about neurological issues in patients who suffer from COVID-19, including stroke, seizures, confusion, dizziness, paralysis, and/or coma. The paper proposes the adoption of a three stage "NeuroCovid" classification scheme to provide a basis from which to build on future hypotheses and investigations regarding SARS-Cov2 and the nervous system. These stages include: NeuroCovid Stage I: The virus damage is limited to epithelial cells of nose and mouth and the main symptoms include transient loss of smell and taste; NeuroCovid Stage II: The virus triggers a cytokine storm, which begins in the lungs and travels in the blood vessels throughout all body organs and leads to the formation of blood clots that cause small or large strokes in the brain; and NeuroCovid Stage III: An explosive level of cytokine storm damages the blood brain barrier, and as a result, blood content, inflammatory markers, and virus particles invade the brain and patients develop seizures, confusion, coma, or encephalopathy. Lead author Majid Fotuhi, medical director of Neurogrow Brain Fitness Center, said more research on COVID-19's long-term effects on the brain is needed and that patients should receive a brain MRI before leaving the hospital. He is also investigating the use of targeted brain training and neurofeedback therapy as part of a brain rehabilitation program for those recovering from COVID-19.
ApoE4’s role in Alzheimer’s blood vessels
The vast majority of Alzheimer’s disease (AD) patients have amyloid deposits in the blood vessels of the brain that damage blood-brain barrier (BBB) function and play a role in cognitive decline. Like for AD itself, the ApoE4 variant is a genetic risk factor for that cerebral amyloid angiopathy (CAA). Researchers from the Massachusetts Institute of Technology (MIT) have shown that ApoE4 increased the risk of CAA through its effects on calcineurin-nuclear factor of activated T cells (calcineurin-NFAT) signaling. In an iPSC-derived model of the BBB, ApoE4-derived cells led to greater accumulation of amyloid beta in the BBB organoid, and that deregulated calcineurin-NFAT signaling. The authors concluded that “our study reveals the role of pericytes in APOE4-mediated CAA and highlights calcineurin-NFAT signaling as a therapeutic target in CAA and Alzheimer’s disease.” They published their results in the June 8, 2020, online issue of Nature Medicine.
Lifespan synaptic atlas gives developmental insights
Scientists at the University of Edinburgh have comprehensively mapped synaptic connections of the mouse brain at different ages, gaining new insights into how synaptic connectivity changes over the lifespan. The team imaged the synaptic connections of mice at 10 different ages, ranging from one day to 18 months. They showed that synapse diversity increased until early adulthood, leading to differentiation of brain regions. Brain regions remained differentiated through midlife, then dedifferentiated, accompanied by enlargement of individual synapses. The authors concluded that changes in synaptic brain architecture “potentially accounts for lifespan transitions in intellectual ability, memory, and susceptibility to behavioral disorders.” The paper was published in the June 12, 2020, issue of Science.