P2-121: Chromosome 21-encoded miRNA-155 upregulation and complement factor H (CFH) deficits in Down syndrome (DS) and Alzheimer's disease (AD)

Abstract Alzheimer’s disease (AD) is the most common cause of dementia. Despite numerous studies on the subject, the pathologies for AD are still unclear and there is still no ideal biomarker for diagnosis. The present study aimed to investigate clinical significance of human complement factor H (CFH) in patients with late-onset AD. Methods: The present prospective study included 187 late-onset AD patients who went to our hospital from January 2015 to December 2017. One hundred patients with mild cognitive impairment (MCI) and 80 healthy individuals who were age and gender matched to AD patients were enrolled as controls. Demographic data such as age, gender, and education duration were recorded. Blood samples were collected and serum levels of C-reactive protein (CRP), CFH, and brain-derived neurotrophic factor (BDNF) were determined by Enzyme-linked immunosorbent assay (ELISA). The mini-mental state examination (MMSE) score was measured for all patients. Results: No significant difference was found in age, gender, and education duration for all participants. The MMSE scores showed AD patients had lower MMES scores than the other two groups. All factors of CFH, CRP, and BDNF were dramatically decreased in AD patients compared with the MCI and the ealthy control. Levels of CFH were found to be positively correlated with levels of CRP; however, no significant correlation was found between CFH and BDNF, nor CFH and MMSE. Conclusion: CFH was decreased in late-onset AD patients, and serum levels of CFH was correlated with serum levels of CRP, but not MMSE and BDNF. These results may provide more clinical evidences for the role of CFH in AD patients.

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Analysis of serum β-amyloid peptides, α2-macroglobulin, complement factor H, and clusterin levels in APP/PS1 transgenic mice during progression of Alzheimer’s disease

Neuroreport ◽

10.1097/wnr.0000000000000661 ◽

2016 ◽

Vol 27 (15) ◽

pp. 1114-1119 ◽

Cited By ~ 7

Author(s):

Dejiang Wang ◽

Xiangjun Di ◽

Lu Fu ◽

Yingnan Li ◽

Xiao Han ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Factor H ◽

Complement Factor H ◽

Complement Factor ◽

Amyloid Peptides ◽

Α2 Macroglobulin ◽

Β Amyloid

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

Human Genetics ◽

10.1007/bf00201718 ◽

1991 ◽

Vol 87 (6) ◽

pp. 649-653 ◽

Cited By ~ 6

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

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Aberrant protein expression of transcription factors BACH1 and ERG, both encoded on chromosome 21, in brains of patients with Down syndrome and Alzheimer’s disease

Advances in Down Syndrome Research - Journal of Neural Transmission Supplement 67 ◽

10.1007/978-3-7091-6721-2_3 ◽

2003 ◽

pp. 39-49 ◽

Cited By ~ 15

Author(s):

K. S. Shim ◽

R. Ferrando-Miguel ◽

G. Lubec

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Down Syndrome ◽

Transcription Factors ◽

Protein Expression ◽

Chromosome 21 ◽

Aberrant Protein

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

Scientific Reports ◽

10.1038/s41598-021-85062-3 ◽

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.

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

10.1101/2021.12.30.474570 ◽

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 .

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