Increased amyloid β protein levels in children and adolescents with Down syndrome

Mehta, Pankaj; Capone, George T.; Jewell, Amy; Freedland, Robert L.

doi:10.1016/j.jns.2006.12.010

Cited by 66 publications

(53 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, there are no APOE genotypes of the individuals participating in the study. However, for patients with DS no correlation between APOE genotype and A ␤ levels has been observed in earlier studies [12][13][14] .…”

Section: Methodsmentioning

confidence: 76%

Increase in β-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome

Englund

Annerén²,

Gustafsson³

et al. 2007

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Background: Individuals with Down syndrome (DS) invariably develop Alzheimer’s disease (AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid-β (Aβ) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change over time. The first CSF sample was taken at 8 months and the following two samples at 20–40 and 54 months of age. Results: Individual levels of the Aβ peptides, as well as total Aβ levels in CSF increased over time when measured with Western blot. Tau in CSF decreased whereas there was no change in levels of phosphorylated tau over time. Conclusion: The increasing levels of Aβ in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the Aβ precursor APP, which leads to an overproduction of Aβ. Despite the increased CSF concentrations of Aβ, there were no signs of an AD-indicating tau pattern in CSF, since the levels of total tau decreased and phosphorylated tau remained unchanged. This observation further strengthens the theory of Aβ pathology preceding tau pathology in AD.

show abstract

Section: Methodsmentioning

confidence: 76%

Increase in β-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome

Englund

Annerén²,

Gustafsson³

et al. 2007

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

show abstract

“…CSF and plasma samples were centrifuged (12,000 g for 10 min at 4°C) prior to the ELISA assay to remove the cell debris. Aβ40 levels in the brain supernatant, CSF and plasma were measured by sandwich ELISA as previously described [26] using 6E10 as capture antibody (anti-human Aβ1–16, Signet Laboratories, USA) and M40 as a detection antibody, kindly provided by Dr. Pankaj Mehta (NYS Institute for Basic Research, New York, N.Y., USA). …”

Section: Animals and Methodsmentioning

confidence: 99%

Direct Exposure of Guinea Pig CNS to Human Luteinizing Hormone Increases Cerebrospinal Fluid and Cerebral Beta Amyloid Levels

Wahjoepramono¹,

Wijaya

Taddei³

et al. 2011

Neuroendocrinology

View full text Add to dashboard Cite

Background/Aims: Luteinizing hormone (LH) has been shown to alter the metabolism of beta amyloid (Aβ), a key protein in Alzheimer’s disease (AD) pathogenesis. While LH and components required for LH receptor signalling are present in the brain, their role in the CNS remains unclear. In vitro, LH has been shown to facilitate neurosteroid production and alter Aβ metabolism. However, whether LH can directly modulate cerebral Aβ levels in vivo has not previously been studied. In this study, we investigated the effect of chronic administration of LH to the guinea pig CNS on cerebral Aβ levels. Methods: Gonadectomised male animals were administered, via cortical placement, either placebo or LH slow-release pellets. At 14 and 28 days after treatment, animals were sacrificed. Brain, plasma and CSF were collected and Aβ levels measured via ELISA. Levels of the Aβ precursor protein (APP) and the neurosteroidogenic enzyme cytochrome P450 side-chain cleavage enzyme (P450scc) were also assayed. Results: An increase in CSF Aβ40 levels was observed 28 days following treatment. These CSF data also reflected changes in Aβ40 levels observed in brain homogenates. No change was observed in plasma Aβ40 levels but APP and its C-terminal fragments (APP-CTF) were significantly increased in response to LH exposure. Protein expression of P450scc was increased after 28 days of LH exposure, suggesting activation of the LH receptor. Conclusion: These data indicate that direct exposure of guinea pig CNS to LH results in altered brain Aβ levels, perhaps due to altered APP expression/metabolism.

show abstract

“…OS occurs within the bilayer, where Aβ(1-42) inserts as oligomers and serves as a source of ROS and initiates LPO (Figure 1) [30]. Deposition of senile plaques is observed in post-mortem brain from DS individuals [33] and levels of both Aβ(1-42) and Aβ(1-40) in plasma are higher in DS compared with non-DS controls [34]. …”

Section: Increased Oxidative Stress In Ds Contributes To Developmementioning

confidence: 99%

HNE-modified proteins in Down syndrome: Involvement in development of Alzheimer disease neuropathology

Barone

Head

Butterfield

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability. The neuropathology of DS involves multiple molecular mechanisms, similar to AD, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylating in neurofibrillary tangles. Interestingly, many genes encoded by chromosome 21, in addition to being primarily linked to amyloid-beta peptide (Aβ) pathology, are responsible for increased oxidative stress (OS) conditions that also result as a consequence of reduced antioxidant system efficiency. However, redox homeostasis is disturbed by overproduction of Aβ, which accumulates into plaques across the lifespan in DS as well as in AD, thus generating a vicious cycle that amplifies OS-induced intracellular changes. The present review describes the current literature that demonstrates the accumulation of oxidative damage in DS with a focus on the lipid peroxidation by-product, 4-hydroxy-2-nonenal (HNE). HNE reacts with proteins and can irreversibly impair their functions. We suggest that among different post-translational modifications, HNE-adducts on proteins accumulate in DS brain and play a crucial role in causing the impairment of glucose metabolism, neuronal trafficking, protein quality control and antioxidant response. We hypothesize that dysfunction of these specific pathways contribute to accelerated neurodegeneration associated with AD neuropathology.

show abstract

Increased amyloid β protein levels in children and adolescents with Down syndrome

Cited by 66 publications

References 40 publications

Increase in β-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome

Increase in β-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome

Direct Exposure of Guinea Pig CNS to Human Luteinizing Hormone Increases Cerebrospinal Fluid and Cerebral Beta Amyloid Levels

HNE-modified proteins in Down syndrome: Involvement in development of Alzheimer disease neuropathology

Contact Info

Product

Resources

About