scholarly journals Pin1 dysregulation helps to explain the inverse association between cancer and Alzheimer's disease

2015 ◽  
Vol 1850 (10) ◽  
pp. 2069-2076 ◽  
Author(s):  
Jane A. Driver ◽  
Xiao Zhen Zhou ◽  
Kun Ping Lu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inverse Association

scholarly journals Evidence of a Causal Association Between Cancer and Alzheimer’s Disease: a Mendelian Randomization Analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sahba Seddighi ◽  
Alexander L. Houck ◽  
James B. Rowe ◽  
Paul D. P. Pharoah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mendelian Randomization ◽  
Observational Evidence ◽  
Inverse Association ◽  
Causal Association ◽  
Lower Odds ◽  
Genetic Predictors ◽  
Log Odds ◽  
Randomization Analysis

Abstract While limited observational evidence suggests that cancer survivors have a decreased risk of developing Alzheimer’s disease (AD), and vice versa, it is not clear whether this relationship is causal. Using a Mendelian randomization approach that provides evidence of causality, we found that genetically predicted lung cancer (OR 0.91, 95% CI 0.84–0.99, p = 0.019), leukemia (OR 0.98, 95% CI 0.96–0.995, p = 0.012), and breast cancer (OR 0.94, 95% CI 0.89–0.99, p = 0.028) were associated with 9.0%, 2.4%, and 5.9% lower odds of AD, respectively, per 1-unit higher log odds of cancer. When genetic predictors of all cancers were pooled, cancer was associated with 2.5% lower odds of AD (OR 0.98, 95% CI 0.96–0.988, p = 0.00027) per 1-unit higher log odds of cancer. Finally, genetically predicted smoking-related cancers showed a more robust inverse association with AD than non-smoking related cancers (OR 0.95, 95% CI 0.92–0.98, p = 0.0026, vs. OR 0.98, 95% CI 0.97–0.995, p = 0.0091).

scholarly journals Are signaling pathways inversely regulated in Alzheimer's disease and glioblastoma multiforme?

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
William G. O'Neal ◽  
Debomoy K. Lahiri, Ph.D ◽  
Mahua Dey, M.D ◽  
Ruizhi Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glioblastoma Multiforme ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Synaptic Proteins ◽  
Low Grade ◽  
Inverse Association ◽  
Potential Impact ◽  
Cell Signaling Pathways

Background: Epidemiological studies suggest an inverse association between cancer and neurodegenerative disorders, including Alzheimer’s disease (AD). AD and cancers, such as glioblastoma multiforme (GBM), are characterized by abnormal but opposing cellular behavior. AD is characterized by accumulation of the processing products of amyloid β (Aβ) and its metabolizing enzymes amyloid precursor protein (APP), β-secretase (or BACE1), and γ-secretase. Our rationale is unraveling cell signaling pathways linking AD and GBM. We hypothesized low-grade gliomas (LGG) and high-grade gliomas (HGG) would have differential expression of neuronal and synaptic markers. Furthermore, protein expression profiles of these markers, APP metabolites, and BACE1 would be different among LGG, HGG, and AD cases.  Experimental Design or project methods: Specific neuronal protein markers (e.g., NSE), presynaptic proteins (e.g., synaptophysin and SNAP25), and post-synaptic proteins (e.g., PSD-95) have been measured in glioma samples. Characterization are done by Western immunoblotting and ELISA. Protein biomarkers will be analyzed in LGG and HGG of biopsy samples, and the results will be compared with brain samples from AD cases.  Results: Using specific primary and secondary antibodies and optimal protein range, we have standardized an immunoblotting procedure to detect our desired proteins in blinded LGG and HGG samples. After unblinding and analyzing results, expression signals will be compared between GBM and AD brain samples.  Conclusion and potential impact: Our results would shed light on diverging and/or shared cell signaling pathways between AD and GBM. In addition, potential impact would be utilizing GBM-derived cultures to test and develop therapeutics for both AD and GBM.

scholarly journals Risk of Alzheimer’s Disease in Cancer Patients: Analysis of Mortality Data from the US SEER Population-Based Registries

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 796 ◽  
Author(s):  
Roman Mezencev ◽  
Yury O. Chernoff
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
White Women ◽  
Mortality Data ◽  
Time Interval ◽  
Cancer Type ◽  
Inverse Association ◽  
The Impact

Previous studies have reported an inverse association between cancer and Alzheimer’s disease (AD), which are leading causes of human morbidity and mortality. We analyzed the SEER (Surveillance, Epidemiology, and End Results) data to estimate the risk of AD death in (i) cancer patients relative to reference populations stratified on demographic and clinical variables, and (ii) female breast cancer (BC) patients treated with chemotherapy or radiotherapy, relative to those with no/unknown treatment status. Our results demonstrate the impact of race, cancer type, age and time since cancer diagnosis on the risk of AD death in cancer patients. While the risk of AD death was decreased in white patients diagnosed with various cancers at 45 or more years of age, it was increased in black patients diagnosed with cancers before 45 years of age (likely due to early onset AD). Chemotherapy decreased the risk of AD death in white women diagnosed with BC at the age of 65 or more, however radiotherapy displayed a more complex pattern with early decrease and late increase in the risk of AD death during a prolonged time interval after the treatment. Our data point to links between molecular mechanisms involved in cancer and AD, and to the potential applicability of some anti-cancer treatments against AD.

scholarly journals Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study

BMJ ◽  
2012 ◽  
Vol 344 (mar12 1) ◽  
pp. e1442-e1442 ◽  
Author(s):  
J. A. Driver ◽  
A. Beiser ◽  
R. Au ◽  
B. E. Kreger ◽  
G. L. Splansky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Framingham Heart Study ◽  
Inverse Association ◽  
Heart Study

scholarly journals Evidence of a Causal Association Between Cancer and Alzheimer’s Disease: a Mendelian Randomization Analysis

2019 ◽  
Author(s):  
Sahba Seddighi ◽  
Alexander L Houck ◽  
James B Rowe ◽  
Paul DP Pharoah
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mendelian Randomization ◽  
Inverse Association ◽  
Lower Odds ◽  
Mendelian Randomization Analysis ◽  
Log Odds ◽  
Randomization Analysis

AbstractObjectivesTo determine whether cancer confers protection against Alzheimer’s disease and to evaluate the relationship in the context of smoking-related cancers versus non-smoking related cancersDesignMendelian randomization analysis using cancer-associated genetic variants as instrumental variablesSettingInternational Genomics of Alzheimer’s ProjectParticipants17,008 Alzheimer’s disease cases and 37,154 controlsMain outcome measuresOdds ratio of Alzheimer’s disease per 1-unit higher log odds of genetically predicted cancerResultsWe found that genetically predicted lung cancer (OR 0.91, 95% CI 0.84-0.99, p=0.019), leukemia (OR 0.98, 95% CI 0.96-0.995, p=0.012), and breast cancer (OR 0.94, 95% CI 0.89-0.99, p=0.028) were associated with 9.0%, 2.4%, and 5.9% lower odds of Alzheimer’s disease, respectively, per 1-unit higher log odds of cancer. When genetic predictors of all cancers were pooled, cancer was associated with 2.5% lower odds of Alzheimer’s disease (OR 0.98, 95% CI 0.96-0.988, p=0.00027) per 1-unit higher log odds of cancer. Finally, genetically predicted smoking-related cancers showed a more robust inverse association with Alzheimer’s disease than non-smoking related cancers (5.2% lower odds, OR 0.95, 95% CI 0.92-0.98, p=0.0026, vs. 1.9% lower odds, OR 0.98, 95% CI 0.97-0.995, p=0.0091).ConclusionsGenetically predicted lung cancer, leukemia, breast cancer, and all cancers in aggregate are associated with lower odds of incident Alzheimer’s disease. Furthermore, the risk of Alzheimer’s disease was lower in smoking-related versus non-smoking related cancers. These results add to the substantial epidemiological evidence of an inverse association between history of cancer and lower odds of Alzheimer’s disease, by suggesting a causal basis for this relationship.

scholarly journals Low plasma neurofilament light levels associated with raised cortical microglial activation suggest inflammation acts to protect prodromal Alzheimer’s disease

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Peter Parbo ◽  
Lasse Stensvig Madsen ◽  
Rola Ismail ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
Mean Diffusivity ◽  
Brain Inflammation ◽  
Translocator Protein ◽  
Inverse Association ◽  
Neurofilament Light ◽  
Amyloid Load ◽  
Β Amyloid

Abstract Background Plasma and cerebrospinal fluid levels of neurofilament light (NfL), a marker of axonal degeneration, have previously been reported to be raised in patients with clinically diagnosed Alzheimer’s disease (AD). Activated microglia, an intrinsic inflammatory response to brain lesions, are also known to be present in a majority of Alzheimer or mild cognitive impaired (MCI) subjects with raised β-amyloid load on their positron emission tomography (PET) imaging. It is now considered that the earliest phase of inflammation may be protective to the brain, removing amyloid plaques and remodelling synapses. Our aim was to determine whether the cortical inflammation/microglial activation load, measured with the translocator protein marker 11C-PK11195 PET, was correlated with plasma NfL levels in prodromal and early Alzheimer subjects. Methods Twenty-seven MCI or early AD cases with raised cortical β-amyloid load had 11C-(R)-PK11195 PET, structural and diffusion magnetic resonance imaging, and levels of their plasma NfL measured. Correlation analyses were performed using surface-based cortical statistics. Results Statistical maps localised areas in MCI cases where levels of brain inflammation correlated inversely with plasma NfL levels. These areas were localised in the frontal, parietal, precuneus, occipital, and sensorimotor cortices. Brain inflammation correlated negatively with mean diffusivity (MD) of water with regions overlapping. Conclusion We conclude that an inverse correlation between levels of inflammation in cortical areas and plasma NfL levels indicates that microglial activation may initially be protective to axons in AD. This is supported by the finding of an inverse association between cortical water diffusivity and microglial activation in the same regions. Our findings suggest a rationale for stimulating microglial activity in early and prodromal Alzheimer cases—possibly using immunotherapy. Plasma NfL levels could be used as a measure of the protective efficacy of immune stimulation and for monitoring efficacy of putative neuroprotective agents.

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