A pilot study on the use of interferon beta-1a in early Alzheimer’s disease subjects

Grimaldi, Luigi Maria Edoardo; Zappalà, Giuseppe; Iemolo, Francesco; Castellano, Anna Elisa; Ruggieri, Stefano; Bruno, Giuseppe; Paolillo, Andrea

doi:10.1186/1742-2094-11-30

Cited by 50 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it is becoming increasingly clear that IFN-I are also involved in a wide range of other neurological diseases including neurodegeneration, ischemia and autoimmune diseases. This is contrasted by other studies that have yielded conflicting results, indicating a neuroprotective role for IFN-I in the murine and human CNS with AD-like neurodegeneration (Ejlerskov et al, 2015;Grimaldi et al, 2014). This study also suggested that IFN-I contribute to the disease in a mouse model for AD (Taylor et al, 2014).…”

Section: Introductioncontrasting

confidence: 88%

“…This study also suggested that IFN-I contribute to the disease in a mouse model for AD (Taylor et al, 2014). This is contrasted by other studies that have yielded conflicting results, indicating a neuroprotective role for IFN-I in the murine and human CNS with AD-like neurodegeneration (Ejlerskov et al, 2015;Grimaldi et al, 2014). Moreover, findings in mouse models for Gaucher disease and Krabbe disease suggest that IFN-I contribute to the neuroinflammation present in some neurodegenerative lysosomal storage diseases (Vitner et al, 2016).…”

mentioning

confidence: 43%

See 1 more Smart Citation

Microglia have a more extensive and divergent response to interferon‐α compared with astrocytes

Wen

Viengkhou

Denyer

et al. 2018

Glia

View full text Add to dashboard Cite

Type I interferons (IFN-I) are crucial for effective antimicrobial defense in the central nervous system (CNS) but also can cause severe neurological disease (termed cerebral interferonopathy) as exemplified by Aicardi-Goutières Syndrome. In the CNS, microglia and astrocytes have essential roles in host responses to infection and injury, with both cell types responding to IFN-I. While the IFN-I signaling pathways are the same in astrocytes and microglia, the extent to which the IFN-I responses of these cells differ, if at all, is unknown. Here we determined the global transcriptional responses of astrocytes and microglia to the IFN-I, IFN-α. We found that under basal conditions, each cell type has a unique gene expression pattern reflective of its developmental origin and biological function. Following stimulation with IFN-α, astrocytes and microglia also displayed a common core response that was characterized by the increased expression of genes required for pathogen detection and elimination. Compared with astrocytes, microglia had a more extensive and diverse response to IFN-α with significantly more genes with expression upregulated (282 vs. 141) and downregulated (81 vs. 3). Further validation was documented for selected IFN-I-regulated genes in a murine model of cerebral interferonopathy. In all, the findings highlight not only overlapping but importantly divergent responses to IFN-I by astrocytes versus microglia. This suggests specialized roles for these cells in host defense and in the development of cerebral interferonopathy.

show abstract

Section: Introductioncontrasting

confidence: 88%

mentioning

confidence: 43%

Microglia have a more extensive and divergent response to interferon‐α compared with astrocytes

Wen

Viengkhou

Denyer

et al. 2018

Glia

View full text Add to dashboard Cite

show abstract

“…Cognitive functions in patients with early AD treated with interferon beta-1 for twenty eight weeks showed mild clinical improvement [33]. This drug is a known anti-viral agent and the above results supported the notion that persistent virus infections may play a role of in AD.…”

Section: Brain Immunity and Adsupporting

confidence: 71%

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Licastro¹,

Porcellini²

2017

Down Syndr Chr Abnorm

View full text Add to dashboard Cite

IntroductionAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Prevalence and incidence of this type of dementia is increasing and extensive research has focused on AD pathogenetic mechanisms to find effective preventive procedures and therapeutic drugs. However, no therapy is available. Therefore, focusing upon diverse aspects of the disease in order to discover new therapeutic strategies appears to be relevant for patients. Moreover, new approaches to the disease's pathogenesis may open innovative prevention opportunities for the elderly or other groups of people without manifest cognitive alterations, but with increased risk of developing dementia.Brain amyloid deposits and intra neuronal neurofibrillary tangles (NFTs) have been suggested as inducers of the disease [1,2]. However, these neuropathological alterations are often also present in the brain of elderly without cognitive alterations or AD pathology [3]. Therefore, it is uncertain whether amyloid or other proteinaceous brain depositions might be causatively linked to AD.The biological role of the amyloid precursor protein (APP) and its proteolytic derivatives (A-beta peptide) in normal brain is still uncertain [4]. However, recent data showed that A-beta peptide is an anti-microbial factor [5]. A recent study reported that the A-beta peptide showed an in vitro anti-virus activity [6]. Therefore, A-beta peptides may play multiple roles in human brain and contribute to antimicroorganism responses.As we elsewhere discussed, genetic data from four genome wide association (GWA) studies on AD [7][8][9] suggested that persistent virus infections may be potentially associated with the age related cognitive decline. In fact, this specific genetic signature may predispose to AD by affecting the individual susceptibility to virus infections [7] during the age associated decline of immune competence. Adults with Down's syndrome (DS) o trisomy of chromosome 21show an elevated risk of cognitive decline and dementia with advancing age. The over expression of the APP gene on the chromosome 21 may lead to an early amyloid deposition in DS brains and be a susceptibility factor for AD [10].Middle age people with DS also show increased tangle brain deposition, neuronal loss and neuro-inflammation along with cerebrovascular pathology [10]. All these factors might accelerate brain aging in DS. A dramatic increase in life expectancy, coupled with a significant reduction in early mortality, has led to a substantial increment in the number of DS subjects reaching old age. This demographic picture parallels increased incidence and prevalence of the age related degenerative diseases in persons with DS.Chronic inflammation is associated with the pathogenesis of most chronic degenerative diseases. In fact, a relevant inflammatory component is always associated with AD, autoimmune diseases, diabetes, atherosclerosis, sarcopenia and cancer. It is of interest that increased levels of circulating inflammatory mediators may be secondary to impaired cytokine resp...

show abstract

“…Grimaldi et al . (110) treated 23 mild‐to‐moderate patients with AD with 22 μg subcutaneous injection of IFN‐β1a, 3 times per week for 28 wk, followed by 24 wk of observation, and compared the effects with those of 19 patients who received placebo. IFN‐β1a was well tolerated, with only rare and mainly mild adverse events.…”

Section: Ifn: Immune Antiviral Activity and Relation To Hsv1 And Admentioning

confidence: 99%

Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts

Itzhaki

2017

FASEB j.

View full text Add to dashboard Cite

Support for the concept that herpes simplex virus type 1 (HSV1), when present in the brains of apolipoprotein E-ε4 carriers, is a major risk for Alzheimer's disease (AD) is increasing steadily, with over 120 publications providing direct or indirect evidence relevant to the hypothesis. No articles have contested the concept, apart from 3 published 13-18 yr ago. This review describes very recent studies on the role of HSV1 but refers also to older studies that provide background for some lesser-known related topics not covered in other recent reviews; these include the relevance of herpes simplex encephalitis and of epilepsy to AD, the action of IFN, and the possible relevance of the different types of DNA damage to AD-in particular, those caused by HSV1-and mechanisms of repair of damage. New epidemiologic data supporting previous studies on mild cognitive impairment and progression to AD are reviewed, as are those examining the relationship between total infectious burden (additive seropositivity to various microbes) and cognition/AD. The latter indicates the involvement of HSV1 and cytomegalovirus (and the necessity of taking into account any marked differences in sensitivity of antibody detection). Recent studies that provide further support for the occurrence of repeated reactivation of latent HSV1 in the brain in AD pathogenesis are also discussed.-Itzhaki, R. F. Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts.

show abstract

A pilot study on the use of interferon beta-1a in early Alzheimer’s disease subjects

Cited by 50 publications

References 24 publications

Microglia have a more extensive and divergent response to interferon‐α compared with astrocytes

Microglia have a more extensive and divergent response to interferon‐α compared with astrocytes

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts

Contact Info

Product

Resources

About