Alzheimer's Disease-Associated beta-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection

作者：Eimer, William A.; Kumar, Deepak Vijaya Kumar; Shanmugam, Nanda Kumar Navalpur; Rodriguez, Alex S.; Mitchell, Teryn; Washicosky, Kevin J.; Gyorgy, Bence; Breakefield, Xandra O.; Tanzi, Rudolph E.^*; Moir, Robert D.^*

来源：Neuron, 2018, 99(1): 56-+.

DOI：10.1016/j.neuron.2018.06.030

• SIMPLEX-VIRUS TYPE-1
• HUMAN ALPHA-DEFENSIN
• CELL-CULTURE MODEL
• ANTIMICROBIAL PEPTIDE
• CATHELICIDIN LL-37
• INNATE IMMUNITY
• SEMENOGELIN-I
• RISK
• OLIGOMERIZATION
• EXPRESSION

Amyloid-beta peptide (A beta) fibrilization and deposition as beta-amyloid are hallmarks of Alzheimer's disease (AD) pathology. We recently reported A beta is an innate immune protein that protects against fungal and bacterial infections. Fibrilization pathways mediate A beta antimicrobial activities. Thus, infection can seed and dramatically accelerate beta-amyloid deposition. Here, we show A beta oligomers bind herpesvirus surface glycoproteins, accelerating beta-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 beta-amyloidosis in brain. These data support the notion that A beta might play a protective role in CNS innate immunity, and suggest an AD etiological mechanism in which herpesviridae infection may directly promote A beta amyloidosis.

• 出版日期2018-7-11