Down Syndrome Biobank Consortium: A perspective

Abstract

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.

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

“…Adults with Down syndrome are participants ideally suited to clinical trials targeting prevention, yet have historically been excluded from trials. However, efforts are underway to provide an optimal infrastructure, centralized research resources and shared expertise that will accelerate the development of effective interventions for individuals with DS, including the “Alzheimer’s Clinical Trials Consortium—Down Syndrome” and the “Down Syndrome Biobank Consortium” [ 157 , 158 ].…”

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

“…Brain pathology assessment was performed on paraffin-embedded cortical and limbic tissue as well as the medulla and spinal cord using a harmonized procedure based upon the NIA-AA protocol [ 6 ] with a few modifications at each site (Lund University, MUSC, UC Irvine, and CU Anschutz). The cases from DSBC were obtained under existing IRBs at each site and using a standard operating procedure [ 3 ]. Brains were carefully removed, and a standard assessment was conducted of the gross anatomy including regional atrophy and inspection of major blood vessels for vascular disease to document potential comorbidities or previous central events of importance for diagnosis.…”

“…Brains were carefully removed, and a standard assessment was conducted of the gross anatomy including regional atrophy and inspection of major blood vessels for vascular disease to document potential comorbidities or previous central events of importance for diagnosis. Brains were photographed from multiple surfaces and sliced in 1 cm coronal slices using a plexiglass brain jig to produce uniform coronal slices at each site [ 3 ]. The slices were placed on a cutting board and photographed prior to microdissection for freezing (left hemisphere) and immersion fixation (right hemisphere) for microscopic analysis.…”

“…The slices were placed on a cutting board and photographed prior to microdissection for freezing (left hemisphere) and immersion fixation (right hemisphere) for microscopic analysis. Right hemisphere slices were fixed in 4% paraformaldehyde for 72 h and transferred to a cryoprotectant solution consisting of 30% sucrose in phosphate buffered saline (PBS) with sodium azide according to a harmonized protocol [ 3 ]. Data regarding time and date of death, date of birth, potential clinical diagnoses, PMI , wet weight of the entire brain, and any special antemortem circumstances such as anxiety or pain were recorded.…”

“…All cases were assigned a randomly generated global unified identifier (GUID). A neuropathology report was conducted on 19 standard brain regions consistent with a modified NIA-AA protocol [ 3 , 43 ]. Dissected fixed brain regions were paraffin embedded [ 65 ], cut at 5-microns and stained for hematoxylin and eosine (H&E), silver impregnation, and immunohistochemistry using alpha-synuclein, amyloid, phospho-tau, TDP43, and other specialty stains according to NIH protocols.…”