Neurological phenotypes for Down syndrome across the life span

Lott, Ira T.

doi:10.1016/b978-0-444-54299-1.00006-6

Cited by 198 publications

(191 citation statements)

References 151 publications

(156 reference statements)

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“…This implies that DS subjects were unable to reliably discriminate between the stimuli and that this deficit was not dependent on the difficulty of the task, at least at the levels presented in the current experiment. These results indicate that deficits in individuals with DS are not limited to cognitive or motor tasks, as is frequently reported in the literature [11,17,46,47], but also extend to processing and perceptual tasks that require recognition and fine discrimination of actions.…”

Section: Discussionsupporting

confidence: 58%

Perception of Biological Motion Speed in Individuals with Down Syndrome

Tolentino-Castro¹,

Riddell²,

Wagner³

2017

J Down Syndr Chr Abnorm

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IntroductionAction and perception are two inherently linked aspects of human behavior that allow us to understand and interact with our surroundings. The interplay between action production and perception enables humans to act in a number of highly demanding situation such as unusual, novel or unstable environments [1]. Babies interact with their environment in a myriad of different ways such as imitation, selfmotion and observing the examples of others [2][3][4]. These interactions serve to shape not only their knowledge about the world, but also their understanding of the functionality of their bodies.Action performance interacts with action perception, and viceversa. This is reflected in the brain, as both performing and perceiving actions activate similar cortical areas [5]. Previous research has revealed significant interactions between action perception and action execution, and studies have shown that action perception can interfere with action execution reciprocally [6][7][8]. It is particularly insightful to study such interactions in populations with abnormal skeleto-muscular and/or neural development, as in these populations the brain may have adapted differently to handle physical differences, which in turn may influence how affected individuals interact with their surroundings. For example Sinha et al. [9] have shown that individuals with autism spectrum disorder, adapt their sensory input atypically, resulting in diverse behavioral traits. Down Syndrome (DS) is one of the most common genetic disorders (14 per 10 000 live births) caused by the presence of a complete or partial third copy of chromosome 21 (Trisomy 21) [10]. DS is a genetic change that impacts not only intellectual ability, but also motor development and motor control over the lifetime [11,12]. Abnormal brain functioning related to learning has been reveled in a number of studies [13][14][15][16]. In addition to neurodevelopmental abnormalities, corporal abnormalities are also common in DS. These abnormalities are highly related to the impaired motor control of voluntary movements [11,17].Children with DS require more time to learn basic movements. Additionally, as movement complexity increases they achieve gross motor functions at an average age that is almost twice that of typically developed children [18]. However, despite delays in motor development and the control of voluntary movements, the DS population does not exhibit a complete absence of the production of gross motor skills. For instance, individuals with DS are often capable of walking and jumping, as well as fine motor skills and manual dexterity. Examples of functional motor development can be seen when special teaching strategies are implemented [19][20][21][22][23][24]. This demonstrates that individuals with DS are at least somewhat able to adapt to their motor impairments. In more realistic tasks, Latash [11,17] argue that, when confronted with an unexpected or unclear motion situation, individuals with DS choose to act slowly (bradykinesia) during the initiation ph...

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Section: Discussionsupporting

confidence: 58%

Perception of Biological Motion Speed in Individuals with Down Syndrome

Tolentino-Castro¹,

Riddell²,

Wagner³

2017

J Down Syndr Chr Abnorm

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“…This cyclical pathway may contribute to neuronal losses during neurogenesis as well as neuronal degeneration in adulthood. Several HSA21 genes have been implicated in generation of ROS including DYRK1A, DSCR1, SOD1, ETS2, S100B, APP and BACH1 [15,17]. Additionally, more recent studies would suggest a synergistic role for various HSA21 genes in induction of this pathological process.…”

Section: Genetic Mechanisms Underlying Oxidative Stress In Dsmentioning

confidence: 99%

Genetic and Epigenetic Mechanisms in Down Syndrome Brain

Lu¹,

Sheen²

2013

Down Syndrome

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“…Down syndrome (DS) is the most common genetic cause of intellectual disability (Shin et al, 2009) and is primarily caused by prenatal changes in central nervous system growth and differentiation (Lott, 2012;Haydar and Reeves, 2012). However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and to the development of Alzheimer's disease (AD) neuropathology.…”

Section: Introductionmentioning

confidence: 99%

“…However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and to the development of Alzheimer's disease (AD) neuropathology. The primary hallmarks of AD, such as the accumulation of amyloid plaques composed of β-amyloid (Aβ) peptides, neurofibrillary tangles (NFTs) formed by insoluble deposits of abnormally hyperphosphorylated tau, neuroinflammation, synapse and neuron loss and regional atrophy, are present in 100% of individuals with DS by the fourth decade of life (Wilcock and Griffin, 2013;Lott, 2012;Cenini et al, 2012;Sabbagh et al, 2011;Lott and Dierssen, 2010;Teipel and Hampel, 2006).…”

Section: Introductionmentioning

confidence: 99%

Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer's disease phenotypes

García-Cerro

Rueda

Vidal

et al. 2017

Neurobiology of Disease

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The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer's disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dualspecificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology. Studies performed in vitro and in vivo in animal models overexpressing this gene have demonstrated that the DYRK1A gene also plays a crucial role in several neurodegenerative processes found in DS. The Ts65Dn (TS) mouse bears a partial triplication of several Hsa21 orthologous genes, including Dyrk1A, and replicates many DS-like abnormalities, including age-dependent cognitive decline, cholinergic neuron degeneration, increased levels of APP and Aβ, and tau hyperphosphorylation. To use a more direct approach to evaluate the role of the gene dosage of Dyrk1A on the neurodegenerative profile of this model, TS mice were crossed with Dyrk1A KO mice to obtain mice with a triplication of a segment of Mmu16 that includes this gene, mice that are trisomic for the same genes but only carry two copies of Dyrk1A, euploid mice with a normal Dyrk1A dosage, and CO animals with a single copy of Dyrk1A. Normalizing the gene dosage of Dyrk1A in the TS mouse rescued the density of senescent cells in the cingulate cortex, hippocampus and septum, prevented cholinergic neuron degeneration, and reduced App expression in the hippocampus, Aβ load in the cortex and hippocampus, the expression of phosphorylated tau at the Ser202 residue in the hippocampus and cerebellum and the levels of total tau in the cortex, hippocampus and cerebellum. Thus, the present study provides further support for the role of the Dyrk1A gene in several AD-like phenotypes found in TS mice and indicates that this gene could be a therapeutic target to treat AD in DS.

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Neurological phenotypes for Down syndrome across the life span

Cited by 198 publications

References 151 publications

Perception of Biological Motion Speed in Individuals with Down Syndrome

Perception of Biological Motion Speed in Individuals with Down Syndrome

Genetic and Epigenetic Mechanisms in Down Syndrome Brain

Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer's disease phenotypes

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