Learning and memory and the underlying cellular correlate, long-term synaptic plasticity, involve regulation by posttranslational modifications (PTMs). Here we demonstrate that conjugation with the small ubiquitin-like modifier (SUMO) is a novel PTM required for normal synaptic and cognitive functioning. Acute inhibition of SUMOylation impairs long-term potentiation (LTP) and hippocampal-dependent learning. Since Alzheimer's disease (AD) prominently features both synaptic and PTM dysregulation, we investigated SUMOylation under pathology induced by amyloid-β (Aβ), a primary neurotoxic molecule implicated in AD. We observed that SUMOylation is dysregulated in both human AD brain tissue and the Tg2576 transgenic AD mouse model. While neuronal activation normally induced upregulation of SUMOylation, this effect was impaired by Aβ42 oligomers. However, supplementing SUMOylation via transduction of its conjugating enzyme, Ubc9, rescued Aβ-induced deficits in LTP and hippocampal-dependent learning and memory. Our data establish SUMO as a novel regulator of LTP and hippocampal-dependent cognition and additionally implicate SUMOylation impairments in AD pathogenesis.

Background: Elsberg syndrome is a rare cause of lumbosacral radiculitis with concomitant thoracic or lumbosacral myelitis that can be seen following an acute or reactivated viral infection. COVID-19 disease, caused by the SARS-CoV-2 virus, has quickly spread to a global pandemic since its rst discovery in the winter of 2019. During this time, there has been an increasing number of case reports describing SARS-CoV-2 associated neuroin ammatory disease.Case Presentation: A 68-year-old man presented in June 2020 with a fall due to progressive lower extremity weakness and numbness, occurring shortly after the initial coronavirus surge in New York City.He developed ascending numbness to the level of the lower abdomen over the preceding month. He subsequently experienced low back pain, and gastrointestinal and genitourinary dysfunction. An extensive laboratory and radiologic evaluation ensued which was notable for elevated SARS-CoV-2 IgG antibodies despite an absence of preceding COVID-19 symptoms. Initial electrodiagnostic testing was notable for absent late responses in the lower extremity nerve conductions with normal distal sensorimotor conductions, and incomplete muscle activation with otherwise normal motor unit morphology and recruitment on electromyography. Repeat testing two weeks later revealed similar nerve conductions, but also the interval development of active neurogenic changes and reduced motor unit recruitment in the L3-L4 myotomes. This was suggestive of a lower thoracic and lumbosacral myelopathy and lumbosacral polyradiculopathy without peripheral neuropathy. A diagnosis of Elsberg syndrome was made and treatment with intravenous methylprednisolone yielded mild clinical improvement and the electrodiagnostic re-emergence of the lower extremity late responses.Conclusions: We report here, to our knowledge, the rst case of suspected COVID-19 associated Elsberg syndrome, which may help to shed light on ways in which to approach diagnostic and treatment options in COVID-19 patients presenting with uncommon neurological and autonomic manifestations.

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