Genetic evidence supporting a causal role of depression on Alzheimer’s disease

2021 ◽  
Author(s):  
Nadia V. Harerimana ◽  
Yue Liu ◽  
Ekaterina S. Gerasimov ◽  
Duc Duong ◽  
Thomas G. Beach ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Evidence ◽  
Causal Role

Time for Well-Powered Controlled Prospective Studies to Test a Causal Role for Herpes Viruses in Alzheimer’s Disease Using Antiherpetic Drugs

2019 ◽  
Vol 75 (6) ◽  
pp. 1058-1060 ◽  
Author(s):  
Pascal J Goldschmidt-Clermont ◽  
Fred G Volinsky ◽  
Steven P LaRosa ◽  
John R Gilbert ◽  
Margaret A Periçak-Vance
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Scientific Evidence ◽  
Phase Iii ◽  
Causal Role ◽  
Herpes Viruses ◽  
Varicella Zoster ◽  
Simplex Virus

AbstractTwenty-six phase III studies on Alzheimer’s disease are ongoing or have been completed in 2018. Most of these studies are targeting amyloid-beta, its production, polymerization, and/or multiple interactions. None of the amyloid-beta studies seem to affect positively the clinical outcome of patients with Alzheimer’s disease thus far, no matter the advancement of disease. It is time to consider other hypotheses for the pathogenesis of Alzheimer’s disease, including the potential role of human herpes viruses (HHV), and especially HHV1 (herpes simplex virus type 1), HHV3 (varicella zoster virus), HHV6A, and HHV7. With this perspective, we review the scientific evidence and make the case for appropriately powered, prospective, randomized, and controlled studies using an anti-HHV drug, to establish a causal role for HHV in Alzheimer’s disease.

scholarly journals Causal effects of circulating cytokine concentrations on risk of Alzheimer’s disease: A bidirectional two-sample Mendelian randomization study

2020 ◽  
Author(s):  
Panagiota Pagoni ◽  
Laura D Howe ◽  
George Davey Smith ◽  
Yoav Ben-Shlomo ◽  
Evie Stergiakouli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Causal Effect ◽  
Causal Effects ◽  
Causal Role ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Weak Evidence ◽  
Increased Risk

ABSTRACTBackgroundThere is considerable interest in the role of neuroinflammation in the pathogenesis of Alzheimer’s disease. Evidence from observational studies suggests an association between cytokine concentrations and Alzheimer’s disease. However, establishing a causal role of cytokine concentrations on risk of Alzheimer’s disease is challenging due to bias from reverse causation and residual confounding.MethodsWe used two-sample MR to explore causal effects of circulating cytokine concentrations on Alzheimer’s disease and vice versa, employing genetic variants associated with cytokine concentrations (N=8,293) and Alzheimer’s disease (71,880 cases / 383,378 controls) from the largest non-overlapping genome-wide association studies (GWAS) of European ancestry.ResultsThere was weak evidence to suggest that 1 standard deviation (SD) increase in levels of CTACK (CCL27) (OR= 1.09 95%CI: 1.01 to 1.19, p=0.03) increased risk of Alzheimer’s disease. There was also weak evidence of a causal effect of 1 SD increase in levels of MIP-1b (CCL4) (OR=1.04 95%CI: 0.99 to 1.09, p=0.08), Eotaxin (OR=1.08 95%CI: 0.99 to 1.17, p =0.10), GROa (CXCL1) (OR=1.04 95%CI: 0.99 to 1.10, p=0.15), MIG (CXCL9) (OR=1.17 95%CI: 0.97 to 1.41, p=0.10), IL-8 (Wald Ratio: OR=1.21 95%CI: 0.97 to 1.51, p=0.09) and IL-2 (Wald Ratio: OR=1.21 95%CI: 0.94 to 1.56, p=0.14) on greater risk of Alzheimer’s disease. There was little evidence of a causal effect of genetic liability to Alzheimer’s disease on circulating cytokine concentrations.ConclusionsOur study provides some evidence supporting a causal role of cytokines in the pathogenesis of Alzheimer’s disease. However, more studies are needed to elucidate the specific mechanistic pathways via which cytokines alter the risk of Alzheimer’s disease.

Dissecting the role of Corticotropin-releasing hormone receptor type 1 in Alzheimer's Disease

2011 ◽  
Vol 44 (06) ◽  
Author(s):  
K Lerche ◽  
M Willem ◽  
K Kleinknecht ◽  
C Romberg ◽  
U Konietzko ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hormone Receptor ◽  
Receptor Type ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

Therapeutic role of MSCs-derived exosomes for Alzheimer's disease.

2020 ◽  
Vol 37 (2) ◽  
pp. 1-12
Author(s):  
Sara M. Kamal ◽  
Aliaa R.H. Mostafa ◽  
Sanaa M.R. Wahba
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Role

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

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