Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection
Authors: Bence György
Alex S Rodriguez
Rudolph E Tanzi
William A Eimer
Robert D Moir
Teryn Mitchell
Kevin J Washicosky
Xandra O Breakefield
Deepak Kumar Vijaya Kumar
Nanda Kumar Navalpur Shanmugam
Journal: Neuron (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Alzheimer’s disease; amyloid-β; antimicrobial peptide; herpes simplex virus 1; herpesviridae
Affiliations: Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA., Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA., Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: .

Abstract:  Amyloid-β peptide (Aβ) fibrilization and deposition as β-amyloid are hallmarks of Alzheimer's disease (AD) pathology. We recently reported Aβ is an innate immune protein that protects against fungal and bacterial infections. Fibrilization pathways mediate Aβ antimicrobial activities. Thus, infection can seed and dramatically accelerate β-amyloid deposition. Here, we show Aβ oligomers bind herpesvirus surface glycoproteins, accelerating β-amyloid deposition and leading to protective viral entrapment activity in 5XFAD mouse and 3D human neural cell culture infection models against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6A and B. Herpesviridae are linked to AD, but it has been unclear how viruses may induce β-amyloidosis in brain. These data support the notion that Aβ might play a protective role in CNS innate immunity, and suggest an AD etiological mechanism in which herpesviridae infection may directly promote Aβ amyloidosis. 

Retracted: No

PubPeer comments:
 Readers and authors should become aware of a preprint entitled  Alzheimer s Disease-Associated u03b2-Amyloid Does Not Protect Against Herpesviridae Brain Infection that is under review in Cell Reports, and could not replicate part of the results from Eimer et al., 2018 study https: papers.ssrn.com sol3 papers.cfm?abstract_id=3628298 From the Abstract:  Alzheimeru2019s disease (AD) is devastating fatal neurodegenerative disease. An alternative to the amyloid cascade hypothesis is the hypothesis that a viral infection is a key to the etiology of late-onset AD with amyloid Au03b2 peptides playing a protective role. **Contrary to previous work, in the current study 5XFAD genotype failed to protect mice against infection with two strains of herpes simplex virus 1 (HSV-1), 17syn+ and McKrae. Moreover, the region- or cell-specific tropisms of HSV-1 were not affected by 5XFAD genotype arguing that the host-pathogen interactions were not altered.Aged 5XFAD mice with abundant Au03b2 showed only a modest, statistically non-significant delay in response to acute HSV-1 infection. While the current study questions the antiviral role of APP or Au03b2, it does not support nor dismiss the hypothesis on viral etiology of late-onset AD.** ,