International Brain Bank for Down Syndrome-Related Alzheimer’s Disease

Principal Investigator

Co-Principal Investigator

Summary

The focus of this special project is to develop a strong collaborate network between six different research groups focused on providing much-needed information about the Down syndrome population, of which as many as 80 percent have Alzheimer’s pathology by the time they are in their 50s and 60s. Although there are many centers and researchers that focus on Alzheimer’s in the general population, few of them focus on people with Down syndrome. The information generated by our project will be of great help to those with Down syndrome and those with Alzheimer’s disease.

Detailed Non-Technical Summary

The long-term goal of this project is to determine the neurobiological mechanisms underlying the onset of Alzheimer's disease (AD) type dementia in Down syndrome (DS).

The first aim of this project is to bank high quality biological research samples, linked to clinical data, from both national and international cohorts of people with DS and dementia, and develop an internationally accepted neuropathological staging protocol for this vulnerable population.

The second goal is to make these samples available to facilitate collaborative research projects into the neurobiological mechanisms of DS-related AD that may also be translatable to the general AD population.

The third goal is to perform collaborative research studies into the early events underlying dementia in people with intellectual disabilities with many different research groups in the USA and Europe, with the specific purpose of developing new therapeutic targets for people with DS and dementia, which may translate to those with AD and other dementias in the general population.

This project is unique in that it is the only funded biobank consortium in the United States focused on people with intellectual disabilities.  The life span of this population has increased over the last few decades, and age is a major factor associated with Alzheimer’s dementia. Few studies have focused on this medically under-investigated group.

See biobank here: https://devdownsbio.wpengine.com/

Publications

Martini AC, Helman AM, McCarty KL, Lott IT, Doran E, Schmitt FA, Head E. Distribution of microglial phenotypes as a function of age and Alzheimer's disease neuropathology in the brains of people with Down syndrome. Alzheimers Dement (Amst). 2020 Oct 14;12(1):e12113. doi: 10.1002/dad2.12113. PMID: 33088896; PMCID: PMC7560512

Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M. Alzheimer's disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 2021 Nov;20(11):930-942. doi: 10.1016/S1474-4422(21)00245-3. PMID: 34687637.

Ledreux A, Thomas S, Hamlett ED, Trautman C, Gilmore A, Rickman Hager E, Paredes DA, Margittai M, Fortea J, Granholm AC. Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain. J Clin Med. 2021 Aug 31;10(17):3931. doi: 10.3390/jcm10173931. PMID: 34501378; PMCID: PMC8432237.

Lemoine L, Ledreux A, Mufson EJ, Perez SE, Simic G, Doran E, Lott I, Carroll S, Bharani K, Thomas S, Gilmore A, Hamlett ED, Nordberg A, Granholm AC. Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue. Mol Neurodegener. 2020 Nov 23;15(1):68. doi: 10.1186/s13024-020-00414-3. PMID: 33222700; PMCID: PMC7682014.

First published on: June 08, 2018

Last modified on: November 27, 2022