scholarly journals Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Donna M. Wilcock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Chromosome 21 ◽  
Pathological Changes ◽  
Genetic Changes ◽  
Course Of Disease ◽  
Complex Process ◽  
Down Syndrome Brain ◽  
The Brain

Down syndrome (DS) is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation in the DS brain and how the genetics of DS may alter this inflammatory response and change the course of disease in the DS brain. The goal of this review is to highlight our current understanding of inflammation in Alzheimer's disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21.

scholarly journals Possible Mechanisms of Tau Spread and Toxicity in Alzheimer’s Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Huiqin Zhang ◽  
Yu Cao ◽  
Lina Ma ◽  
Yun Wei ◽  
Hao Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cellular Uptake ◽  
Current Evidence ◽  
Pathological Changes ◽  
Tau Pathology ◽  
Complex Process ◽  
Growing Body ◽  
The Brain

Tau is a protein that associates with microtubules (MTs) and promotes their assembly and stability. The protein loses its ability to bind MTs in tauopathies, and detached tau can misfold and induce the pathological changes that characterize Alzheimer’s disease (AD). A growing body of evidence indicates that tauopathies can spread between cells or connected regions. Pathological tau transmission in the brain of patients with AD and other tauopathies is due to the spread of various tau species along neuroanatomically connected regions in a “prion-like” manner. This complex process involves multiple steps of secretion, cellular uptake, transcellular transfer, and/or seeding, but the precise mechanisms of tau pathology propagation remain unclear. This review summarizes the current evidence on the nature of propagative tau species and the possible steps involved in the process of tau pathology spread, including detachment from MTs, degradations, and secretion, and discusses the different mechanisms underlying the spread of tau pathology.

Identification of chromosome 21 DNA polymorphisms for genetic studies in Alzheimer's disease and Down syndrome

1991 ◽  
Vol 87 (6) ◽  
pp. 649-653 ◽  
Author(s):  
G. Van Camp ◽  
H. Backhovens ◽  
M. Cruts ◽  
A. Wehnert ◽  
W. Van Hul ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Chromosome 21 ◽  
Dna Polymorphisms ◽  
Genetic Studies

Expression of two novel β-secretase-candidate aspartyl proteases in Alzheimer's disease and down syndrome brain

2000 ◽  
Vol 21 ◽  
pp. 119
Author(s):  
David R. Howlett ◽  
Carol W. Gray ◽  
Ishrut Hussain ◽  
David J. Powell ◽  
Julie Hawkins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Down Syndrome Brain ◽  
Aspartyl Proteases

scholarly journals Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Justin L. Tosh ◽  
◽  
Elena R. Rhymes ◽  
Paige Mumford ◽  
Heather T. Whittaker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Precursor Protein ◽  
Mouse Models ◽  
Early Onset ◽  
Amyloid Β ◽  
Chromosome 21 ◽  
Extra Copy ◽  
Early Onset Alzheimer’S Disease

AbstractIndividuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.

scholarly journals Endosomal structure and APP biology are not altered in preclinical cellular models of Down syndrome

2021 ◽  
Author(s):  
Claudia Cannavo ◽  
Karen Cleverley ◽  
Cheryl Maduro ◽  
Paige Mumford ◽  
Dale Moulding ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Cell Biology ◽  
Amyloid Β ◽  
Chromosome 21 ◽  
App Processing ◽  
Cellular Models ◽  
Increased Risk ◽  
Primary Mouse

Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer’s disease – dementia. Alzheimer’s disease is characterised by the accumulation in the brain of amyloid-β plaques that are a product of amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes and changes to endosome biology occur early in disease. Here we determine if primary mouse embryonic fibroblasts isolated from two mouse models of Down syndrome can be used to study endosome and APP cell biology. We report that in these cellular models of Down syndrome endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in these models, despite three copies of App .

scholarly journals β-Secretases, Alzheimer’s Disease, and Down Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Robin L. Webb ◽  
M. Paul Murphy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Precursor Protein ◽  
Healthy Aging ◽  
Precursor Protein ◽  
Chromosome 21 ◽  
Rate Limiting Step ◽  
Age Related

Individuals with Down Syndrome (DS), or trisomy 21, develop Alzheimer’s disease (AD) pathology by approximately 40 years of age. Chromosome 21 harbors several genes implicated in AD, including the amyloid precursor protein and one homologue of theβ-site APP cleaving enzyme, BACE2. Processing of the amyloid precursor protein byβ-secretase (BACE) is the rate-limiting step in the production of the pathogenic Aβpeptide. Increased amounts of APP in the DS brain result in increased amounts of Aβand extracellular plaque formation beginning early in life. BACE dysregulation potentially represents an overlapping biological mechanism with sporadic AD and a common therapeutic target. As the lifespan for those with DS continues to increase, age-related concerns such as obesity, depression, and AD are of growing concern. The ability to prevent or delay the progression of neurodegenerative diseases will promote healthy aging and improve quality of life for those with DS.

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