scholarly journals Alzheimer’s Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N  =  395,769)

2020 ◽  
pp. 1-11
Author(s):  
Amy C. Ferguson ◽  
Rachana Tank ◽  
Laura M. Lyall ◽  
Joey Ward ◽  
Carlos Celis-Morales ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Disease Susceptibility ◽  
Susceptibility Gene ◽  
Uk Biobank ◽  
Blood Biomarkers ◽  
Disease Susceptibility Gene

scholarly journals Alzheimer’s disease susceptibility gene apolipoprotein e (APOE) and blood biomarkers in UK Biobank (N=395,769)

2020 ◽  
Author(s):  
Amy C. Ferguson ◽  
Rachana Tank ◽  
Laura M. Lyall ◽  
Joey Ward ◽  
Carlos Celis-Morales ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Apolipoprotein E ◽  
Genetic Risk ◽  
Susceptibility Gene ◽  
Density Lipoprotein ◽  
European Ancestry ◽  
Uk Biobank ◽  
Blood Biomarkers

AbstractBackground and objectiveAlzheimer’s disease (AD) is a neurodegenerative condition where the underlying aetiology is still unclear. Investigating the potential influence of apolipoprotein e (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk. Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.MethodsAfter quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.ResultsSeveral biomarkers significantly associated with APOE e4 ‘risk’ and e2 ‘protective’ genotypes (vs. neutral e3/e3). Most associations supported previous data: for example, e4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p<0.001) and e2 with lower LDL (b = −0.456 SDs, p<0.001). There were however instances of associations found in unexpected directions: e.g. e4 and increased insulin-like growth factor (IGF-1) (standardized beta = 0.017, p<0.001) where lower levels have been previously suggested as an AD risk factor.ConclusionsThese findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence here in supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.

P4-245: The Alzheimer's disease susceptibility gene CALHM1 encodes a brain calcium channel

2008 ◽  
Vol 4 ◽  
pp. T743-T743
Author(s):  
Ute Dreses-Werringloer ◽  
Jean-Charles Lambert ◽  
Valérie Vingtdeux ◽  
Haitian Zhao ◽  
Horia Vais ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Calcium Channel ◽  
Disease Susceptibility ◽  
Susceptibility Gene ◽  
Disease Susceptibility Gene

scholarly journals P3-126: FUNCTIONAL DISSECTION OF AN ALZHEIMER'S DISEASE SUSCEPTIBILITY GENE NETWORK

2019 ◽  
Vol 15 ◽  
pp. P978-P979
Author(s):  
Tom V. Lee ◽  
Katherine S. Allison ◽  
Shamsideen A. Ojelade ◽  
James J. Lah ◽  
Allan I. Levey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Network ◽  
Disease Susceptibility ◽  
Susceptibility Gene ◽  
Disease Susceptibility Gene

[O2-18-04]: THE ALZHEIMER's DISEASE SUSCEPTIBILITY GENE CD2AP REGULATES PRESYNAPTIC FUNCTION

2017 ◽  
Vol 13 (7S_Part_12) ◽  
pp. P603-P603 ◽  
Author(s):  
Shamsideen A. Ojelade ◽  
Tom V. Lee ◽  
Nikolaos Giagtzoglou ◽  
Joshua M. Shulman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Susceptibility ◽  
Susceptibility Gene ◽  
Presynaptic Function ◽  
Disease Susceptibility Gene

scholarly journals Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer’s disease

2016 ◽  
Vol 37 (1) ◽  
pp. 217-226 ◽  
Author(s):  
Ai-Ling Lin ◽  
Jordan B Jahrling ◽  
Wei Zhang ◽  
Nicholas DeRosa ◽  
Vikas Bakshi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Human Subjects ◽  
Susceptibility Gene ◽  
Learning Deficits ◽  
Cerebrovascular Function

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E ɛ4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E ɛ4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer's disease intervention studies in human subjects.

scholarly journals The Neurochemistry of Alzheimer’s Disease: One of the Most Common Causes of Reduced Capability in the Adult Population

2022 ◽  
pp. 81-93
Author(s):  
Kaj Blennow ◽  
Henrik Zetterberg
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Susceptibility Gene ◽  
Tau Pathology ◽  
Blood Biomarkers ◽  
Neurofilament Light ◽  
Risk Profiling ◽  
Lifestyle Risk ◽  
Intervention Trials

AbstractAlzheimer’s disease (AD) is the most common form of dementia and is characterised by the triad of amyloid plaques, tau pathology and neurodegeneration. Except for a strong association with the susceptibility gene, specifically the apolipoprotein E (APOE) ε4 allele, the pathogenesis of the most common age-related sporadic form of AD is largely unknown. However, several genetic and environmental risk factors have been proposed. A potential problem is that most population-based studies on AD risk-profiling have not used biomarkers reflecting amyloid and tau pathology to classify patients and controls. Given the complex pathophysiology of late-onset AD and the difficulties in correctly diagnosing AD on purely clinical grounds, this introduces a risk of misclassification of both control subjects and clinically diagnosed AD cases. Importantly, in recent years, there has been a very successful development of blood biomarkers for AD pathophysiologies, including brain amyloidosis (amyloid β ratio), tau pathology (phosphorylated tau) and neurodegeneration (neurofilament light). Numerous studies have shown these biomarkers to correlate with amyloid and tau pathology load evaluated by PET and with MRI measures of neurodegeneration, and to predict future cognitive decline. The employment of blood biomarkers in epidemiological studies may foster an understanding of which and how specifically lifestyle risk factors are linked to AD, and repeated blood sampling in intervention trials may provide evidence as to whether controlling lifestyle factors may affect specific AD pathophysiologies.

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