Structural Connectivity in Down Syndrome and Alzheimer’s Disease

TY - JOUR

T1 - Structural Connectivity in Down Syndrome and Alzheimer’s Disease

AU - Saini, Fedal

AU - Dell' Acqua, Flavio

AU - Strydom, Andre

N1 - Funding Information: This study was supported by funding from the Medical Research Council, Grant/Award Numbers: MRCMR/S011277/1, MR/S005145/1, and MR/R024901/1. Publisher Copyright: Copyright © 2022 Saini, Dell’Acqua and Strydom.

PY - 2022/7/22

Y1 - 2022/7/22

N2 - Down syndrome (DS) arises from the triplication of chromosome 21, which leads to an atypical neurodevelopment and the overproduction of the amyloid precursor protein, predisposing to early Alzheimer’s disease (AD). Not surprisingly, trisomy 21 is widely considered a model to study predementia stages of AD. After decades, in which neural loss was the main focus, research in AD is now moving toward understanding the neurodegenerative aspects affecting white matter. Motivated by the development of magnetic resonance imaging (MRI)-based diffusion techniques, this shift in focus has led to several exploratory studies on both young and older individuals with DS. In this review, we synthesise the initial efforts made by researchers in characterising in-vivo structural connectivity in DS, together with the AD footprint on top of such pre-existing connectivity related to atypical brain development. The white matter structures found to be affected in DS are the corpus callosum and all the main long-association fibres, namely the inferior fronto-occipital fasciculus, the inferior and superior longitudinal fasciculus, the uncinate fasciculus and the cingulum bundle. Furthermore, the cingulum bundle and the corpus callosum appear to be particularly sensitive to early AD changes in this population. Findings are discussed in terms of their functional significance, alongside methodological considerations and implications for future research.

AB - Down syndrome (DS) arises from the triplication of chromosome 21, which leads to an atypical neurodevelopment and the overproduction of the amyloid precursor protein, predisposing to early Alzheimer’s disease (AD). Not surprisingly, trisomy 21 is widely considered a model to study predementia stages of AD. After decades, in which neural loss was the main focus, research in AD is now moving toward understanding the neurodegenerative aspects affecting white matter. Motivated by the development of magnetic resonance imaging (MRI)-based diffusion techniques, this shift in focus has led to several exploratory studies on both young and older individuals with DS. In this review, we synthesise the initial efforts made by researchers in characterising in-vivo structural connectivity in DS, together with the AD footprint on top of such pre-existing connectivity related to atypical brain development. The white matter structures found to be affected in DS are the corpus callosum and all the main long-association fibres, namely the inferior fronto-occipital fasciculus, the inferior and superior longitudinal fasciculus, the uncinate fasciculus and the cingulum bundle. Furthermore, the cingulum bundle and the corpus callosum appear to be particularly sensitive to early AD changes in this population. Findings are discussed in terms of their functional significance, alongside methodological considerations and implications for future research.

KW - Down Syndrome

KW - Trisomy 21

KW - Alzheimer disease

KW - White matter

KW - structural connectivity

KW - diffusion tensor imaging (DTI)

KW - Tract based special statistic (TBSS)

KW - functional connectivity

UR - http://www.scopus.com/inward/record.url?scp=85135447406&partnerID=8YFLogxK

U2 - 10.3389/fnins.2022.908413

DO - 10.3389/fnins.2022.908413

M3 - Review article

SN - 1662-453X

VL - 16

JO - Frontiers in Neuroscience

JF - Frontiers in Neuroscience

M1 - 908413

ER -