The Prevalence of Dementia in Down Syndrome

Johannsen, Peter; Christensen, Johnny; Mai, Jesper

doi:10.1159/000106883

Cited by 15 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Table 1, which shows an exponential increase of dementia with age, illustrates this increase of dementia with age. Holland et al (1998) and Johannsen et al (1996) have both reported age-related increases in prevalence in two population studies of dementia in DS.…”

Section: Discussionmentioning

confidence: 97%

Dementia in people with Down's syndrome

Tyrrell

Cosgrave

McCarron

et al. 2001

Int J Geriat Psychiatry

149

128

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 97%

Dementia in people with Down's syndrome

Tyrrell

Cosgrave

McCarron

et al. 2001

Int J Geriat Psychiatry

149

128

View full text Add to dashboard Cite

show abstract

“…As individuals with DS age, they have an increased risk for cognitive decline, dementia, and Alzheimer’s disease (AD) [3, 4]. This risk is likely due to the genetic imbalance present in DS: triplication and overexpression of genes located on chromosome 21, such as APP, SOD1 , and BACE2 [5].…”

Section: Introductionmentioning

confidence: 99%

Early and Selective Activation and Subsequent Alterations to the Unfolded Protein Response in Down Syndrome Mouse Models

Lanzillotta

Tramutola

Meier

et al. 2018

JAD

View full text Add to dashboard Cite

Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. DS individuals have an increased risk of developing Alzheimer’s disease (AD)-like pathology and dementia by the age of 40 due to the triplication of several genes involved in the formation of amyloid plaques and tau tangles. Further, DS and AD are characterized by the aberrant accumulation of unfolded/misfolded proteins resulting from over-burdened protein quality control systems. The accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers a cellular stress response called the unfolded protein response (UPR). Long-term activation of the UPR mediates neuronal dysfunction in AD. We hypothesized that the UPR is impacted in a mouse model of DS. To test this, we performed gene and protein expression analysis of ER stress markers in the Ts65Dn mouse model of DS at 3, 9, and 18 months. We identified activation of the PERK pathway in Ts65Dn DS mice at 3 months of age compared to euploid controls. We also determined that the early and overt UPR activation decreased with age, the UPR signal was significantly reduced by 18 months. Our data suggest that UPR activation in DS mouse models occurs early before consistent brain neurodegeneration and might be an essential contributor to dys-proteostasis.

show abstract

“…The vast majority of DS individuals over the age of 40 will develop significant amyloid pathology that is indistinguishable from Alzheimer's disease (AD) including beta-amyloid (Aβ) plaques and neurofibrillary tangles (Leverenz and Raskind, 1998, Wisniewski, et al, 1985). By 50-60 years many, but not all, of these individuals will develop dementia (Johannsen, et al, 1996, Schupf and Sergievsky, 2002). With the emergence of anti-amyloid agents as potential preventative therapies for AD, there is excitement in the field regarding the translation of these approaches to people with DS.…”

Section: Introductionmentioning

confidence: 99%

Down syndrome individuals with Alzheimer's disease have a distinct neuroinflammatory phenotype compared to sporadic Alzheimer's disease

Wilcock

Hurban

Helman

et al. 2015

Neurobiology of Aging

View full text Add to dashboard Cite

Down syndrome (DS) is the most common genetic cause of intellectual disability and is primarily caused by the triplication of chromosome 21. The overexpression of APP may be sufficient to overexpression's disease (AD) neuropathology that is observed in virtually all individuals with DS by the age of 40 years. There is relatively little information about inflammation in the DS brain and how the genetics of DS may alter inflammatory responses and modify the course of AD pathogenesis in this disorder. Using the macrophage classification system of M1, M2a, M2b and M2c inflammatory phenotypes we have shown that the early stages of AD are associated with a bias toward an M1 or M2a phenotype. In later stages of AD, markers of M1, M2a and M2c are elevated. We now report the inflammatory phenotype in a DS autopsy series to compare this with the progression in sporadic AD. Tissue from young DS cases (under 40 years of age, pre-AD) show a bias toward M1 and M2b states with little M2a or M2c observed. Older DS cases (over 40 with AD pathology) show a distinct bias toward an M2b phenotype. Importantly, this is distinct from sporadic AD where the M2b phenotype has been rarely, if ever observed in post-mortem studies. Stimulated by immune complex activation of microglial cells and toll-like receptor activation, the M2b phenotype represents a unique neuroinflammatory state in diseased brain and may have significant implications for therapeutic intervention for persons with DS.

show abstract

The Prevalence of Dementia in Down Syndrome

Cited by 15 publications

References 18 publications

Dementia in people with Down's syndrome

Dementia in people with Down's syndrome

Early and Selective Activation and Subsequent Alterations to the Unfolded Protein Response in Down Syndrome Mouse Models

Down syndrome individuals with Alzheimer's disease have a distinct neuroinflammatory phenotype compared to sporadic Alzheimer's disease

Contact Info

Product

Resources

About