A reduced risk of Alzheimer's disease in those who survive cancer

BMJ ◽  
2012 ◽  
Vol 344 (mar12 1) ◽  
pp. e1662-e1662 ◽  
Author(s):  
M. Ganguli
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reduced Risk

scholarly journals A Genetic Variant of the Sortilin 1 Gene is Associated with Reduced Risk of Alzheimer’s Disease

2016 ◽  
Vol 53 (4) ◽  
pp. 1353-1363 ◽  
Author(s):  
Carl-Henrik Andersson ◽  
Oskar Hansson ◽  
Lennart Minthon ◽  
Niels Andreasen ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variant ◽  
Reduced Risk

scholarly journals Use of diuretics is associated with reduced risk of Alzheimer's disease: the Cache County Study

2014 ◽  
Vol 35 (11) ◽  
pp. 2429-2435 ◽  
Author(s):  
Yi-Fang Chuang ◽  
John C.S. Breitner ◽  
Yen-Ling Chiu ◽  
Ara Khachaturian ◽  
Kathleen Hayden ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cache County ◽  
Reduced Risk

scholarly journals Clonal Hematopoiesis is Associated with Reduced Risk of Alzheimer's Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5-5
Author(s):  
Hind Bouzid ◽  
Julia Belk ◽  
Max Jan ◽  
Yanyan Qi ◽  
Chloé Sarnowski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Genome Wide Association Studies ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Two Samples ◽  
Mutant Cells ◽  
The Brain ◽  
Reduced Risk

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) occurs when hematopoietic stem cells (HSCs) acquire a mutation, most commonly a null variant in TET2 or DNMT3A, that confers a selective advantage. Blood cancers may result if additional cooperating mutations are acquired. However, CHIP may also cause atherosclerosis and other inflammatory diseases because these mutations alter the function or development of effector immune cells derived from the HSCs. Genome-wide association studies have implicated microglia, the resident myeloid cells in the brain, as key players in the biology of Alzheimer's disease (AD). Here, we asked whether CHIP associated with AD dementia or neuropathologic change, and whether mutant marrow-derived cells could be found in the brains of CHIP carriers. To test for an association, we used data from the Trans-omics for Precision Medicine project (TOPMed) and the Alzheimer's Disease Sequencing Project (ADSP), where whole genome or exome sequencing data as well as AD phenotype data was available on 5,730 persons. TOPMed contained population-based cohorts unselected for AD, while ADSP was a case-control study for AD. We surprisingly discovered that the presence of CHIP was associated with a reduced risk of AD dementia in both projects (fixed-effects meta-analysis odds ratio 0.64, p = 3.0 x 10-5, adjusted for age, sex and APOE genotype) (Figure 1). The protective effect of CHIP was strongest in those with APOE e3 or e4 alleles, but not seen in those with APOE e2 allele. No substantial differences in AD risk were seen based on mutated driver gene. In addition, the presence of CHIP was associated with a reduced burden of amyloid plaques and neurofibrillary tangles in the brains of those without dementia. In sum, our human genetic analyses indicated that CHIP was robustly associated with protection from AD dementia and AD-related neuropathologic changes. A causal link between CHIP and AD would be strengthened by finding the mutated cells infiltrating the brain. However, it is presumed that bone marrow progenitors have minimal contribution to the adult microglial pool. To determine if the mutations seen in the blood of CHIP carriers could also be found in the brain, we obtained 8 occipital cortex samples from autopsy of donors with CHIP, 6 of whom were cognitively normal at the time of death. The 8 CHIP carriers had mutations in DNMT3A, TET2, ASXL1, SF3B1, and GNB1 with the highest frequency in DNMT3A and TET2, which is representative of the relative proportion of these mutations in the general population. We detected the CHIP somatic variants in the microglia enriched (NeuN- c-Maf+) fraction of brain in 7 out of 8 CHIP carriers, with a VAF ranging from 0.02 to 0.28 (representing 4% to 56% of nuclei) (Figure 2), but at low levels or absent in the other fractions of brain. We then performed single-cell ATAC-sequencing on brain samples from 2 CHIP carriers and 1 control to specify the cellular population harboring CHIP mutations. This revealed that hematopoietic cells in the 3 samples formed a single myeloid cluster that had accessible chromatin at the microglia marker genes TMEM119, P2RY12, and SALL1, but not in genes specific to monocytes or dendritic cells. We further determined that the proportion of cells in this cluster bearing the CHIP mutations ranged from ~40-80% in these two samples, indicating widespread replacement of the endogenous microglial pool by mutant cells. We show here that, unexpectedly, the presence of CHIP is associated with protection from AD dementia. CHIP is also associated with lower levels of neuritic plaques and neurofibrillary tangles in those without dementia, indicating a possible modulating effect of CHIP on the underlying pathophysiology of AD. Consistent with this hypothesis, we also detect substantial infiltration of brain by marrow-derived mutant cells which adopt a microglial-like phenotype. We speculate that the mutations associated with CHIP confer circulating precursor cells with an enhanced ability to engraft in the brain, to differentiate into microglia once engrafted, and/or to clonally expand relative to unmutated cells in the brain microenvironment. These non-mutually exclusive possibilities could provide protection from AD by supplementing the phagocytic capacity of the endogenous microglial system during aging. Figure 1 Figure 1. Disclosures Jaiswal: Novartis: Consultancy, Honoraria; Foresite Labs: Consultancy; Genentech: Consultancy, Honoraria; AVRO Bio: Consultancy, Honoraria; Caylo: Current holder of stock options in a privately-held company.

scholarly journals Bladder Cancer Immunotherapy by BCG Is Associated with a Significantly Reduced Risk of Alzheimer‘s Disease and Parkinson’s Disease

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 491
Author(s):  
Danielle Klinger ◽  
Brian L. Hill ◽  
Noam Barda ◽  
Eran Halperin ◽  
Ofer N. Gofrit ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Bladder Cancer ◽  
Beneficial Effect ◽  
Neurodegenerative Diseases ◽  
P Value ◽  
Protective Agent ◽  
Reduced Risk

Bacillus Calmette–Guerin (BCG) is a live attenuated form of Mycobacterium bovis that was developed 100 years ago as a vaccine against tuberculosis (TB) and has been used ever since to vaccinate children globally. It has also been used as the first-line treatment in patients with nonmuscle invasive bladder cancer (NMIBC), through repeated intravesical applications. Numerous studies have shown that BCG induces off-target immune effects in various pathologies. Accumulating data argue for the critical role of the immune system in the course of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this study, we tested whether repeated exposure to BCG during the treatment of NMIBC is associated with the risk of developing AD and PD. We presented a multi-center retrospective cohort study with patient data collected between 2000 and 2019 that included 12,185 bladder cancer (BC) patients, of which 2301 BCG-treated patients met all inclusion criteria, with a follow-up of 3.5 to 7 years. We considered the diagnosis date of AD and nonvascular dementia cases for BC patients. The BC patients were partitioned into those who underwent a transurethral resection of the bladder tumor followed by BCG therapy, and a disjoint group that had not received such treatment. By applying Cox proportional hazards (PH) regression and competing for risk analyses, we found that BCG treatment was associated with a significantly reduced risk of developing AD, especially in the population aged 75 years or older. The older population (≥75 years, 1578 BCG treated, and 5147 controls) showed a hazard ratio (HR) of 0.726 (95% CI: 0.529–0.996; p-value = 0.0473). While in a hospital-based cohort, BCG treatment resulted in an HR of 0.416 (95% CI: 0.203–0.853; p-value = 0.017), indicating a 58% lower risk of developing AD. The risk of developing PD showed the same trend with a 28% reduction in BCG-treated patients, while no BCG beneficial effect was observed for other age-related events such as Type 2 diabetes (T2D) and stroke. We attributed BCG’s beneficial effect on neurodegenerative diseases to a possible activation of long-term nonspecific immune effects. We proposed a prospective study in elderly people for testing intradermic BCG inoculation as a potential protective agent against AD and PD.

Cognitive Activity and Risk of Alzheimer's Disease

2003 ◽  
Vol 12 (3) ◽  
pp. 87-91 ◽  
Author(s):  
Robert S. Wilson ◽  
David A. Bennett
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Old Age ◽  
Cognitive Activity ◽  
Occupational Attainment ◽  
Epidemiological Evidence ◽  
Reduce Risk ◽  
Higher Educational ◽  
Reduced Risk

Recent research suggests that frequent participation in cognitively stimulating activities may reduce risk of Alzheimer's disease in old age. We review epidemiological evidence of such an association. We then consider whether cognitive activity can account for the association between higher educational and occupational attainment and reduced risk of Alzheimer's disease. Finally, we discuss the behavioral and neurobiological mechanisms that may underlie the association between cognitive activity and risk of Alzheimer's disease.

P1-077: A novel ARC polymorphism is associated with reduced risk of Alzheimer's disease

2010 ◽  
Vol 6 ◽  
pp. S196-S196
Author(s):  
Petronella Kettunen ◽  
Sara Landgren ◽  
Malin Von Otter ◽  
Staffan Nilsson ◽  
Mona Seibt Palmér ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reduced Risk

P3-175: A reduced risk of Alzheimer's disease is associated with the majority of cancers in a national cohort of veterans

2013 ◽  
Vol 9 ◽  
pp. P617-P617 ◽  
Author(s):  
Laura Frain ◽  
David Swanson ◽  
Rebecca Betensky ◽  
Kelly Cho ◽  
David Gagnon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
National Cohort ◽  
Reduced Risk
Sign in / Sign up

Export Citation Format

Share Document