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 (Aß), 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). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aß deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

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. Of the genetic causes of AD, people with DS represent the largest cohort. Currently, there is a knowledge gap regarding the underlying neurobiological mechanisms of DS-related AD (DS-AD), partly due to limited access to well-characterized brain tissue and biomaterials for research. To address this challenge, we created an international consortium of brain banks focused on collecting and disseminating brain tissue from persons with DS throughout their lifespan, named the Down Syndrome Biobank Consortium (DSBC) consisting of 11 biobanking sites located in Europe, India, and the USA. This perspective describes the DSBC harmonized protocols and tissue dissemination goals.

Urothelial carcinoma metastases impacting the CNS: A 20-year retrospective series.

INTRODUCTION: Our group has a longstanding interest in metastases impacting the central nervous system (CNS), including spread from prostatic adenocarcinomas, thyroid carcinomas, and breast carcinomas, most of which metastasize to CNS sites at a later time after the primary tumor is well-known. However, one of the least frequent types of systemic malignancies to metastasize to brain or spine is urothelial carcinoma. Thus, few large studies from a single institution exist. Fewer still detail the interval between first diagnosis of primary tumor and CNS lesion, or whether a patient might have their first presentation of cancer in the brain or spine, thus prompting review of our 20-year experience. MATERIALS: Case identification via text word search of pathology databases from our adult and referral hospitals, 2002 to present. Demographic and clinical data were extracted from reports and the medical record. RESULTS: 15 cases, 11 male: 4 female, age range 37-82 years were identified. Nine had metastases to brain parenchyma, 5 to vertebral column impacting spinal cord, and 2 to skull, one of which had tumor extension into right parietal lobe. Strikingly, 5 of 15 patients had had their CNS-impacting metastasis as their first presentation of neoplastic disease. CONCLUSIONS: CNS metastasis of urothelial carcinoma is a rare occurrence; nevertheless, pathologists should include urothelial carcinoma in their differential diagnosis as a type of cancer that can first present with a CNS-impacting metastasis.