Recent scientific reports, one in the journal Neuron and another coming out in the journal Cell, present some intriguing new data indicating a link between human herpes viruses and Alzheimer’s disease (AD). Because the majority of AD cases cannot be attributed to genetics alone, there has been keen interest in finding other factors that affect the risk of developing AD. Head trauma and infections are two such factors that have received attention by researchers. With regard to infectious agents, speculation has often centered on the herpes viruses, especially herpes simplex virus 1 (HSV1). Human herpes viruses are neurotropic, which means they have an affinity for nerve cells. In fact, UCI MIND Faculty members Drs. David Cribbs, Carl Cotman and Frank LaFerla published a paper in 2000 in the journal Biochemistry where they showed HSV1, which is extremely common and causes cold sores, includes a small region that is very similar to amyloid peptide that accumulates in neuritic plaques in AD brains. Surprisingly, when they tested the virus in laboratory studies, it had many of the properties of amyloid, including killing nerve cells growing in a dish. In the more recent study, increased levels of two human herpes viruses (HHV-6A & HHV-7) were found in AD brain tissue when compared to brains from controls. The authors of those study also found that AD progression correlates with increased virus levels across multiple brain regions.
In the forthcoming Cell publication, investigators have extended the UCI report and shown that herpes virus induces Aβ peptide aggregation into plaque-like structures. Moreover, herpes virus infection rapidly seeds amyloid plaque deposition in a transgenic mouse model of AD and in 3-dimensional human neural cell cultures.
Collectively, these research reports provide support for the hypothesis that herpes viruses may be a risk factor for AD, though many in the field are recommending caution when interpreting these results. In particular, the recent studies in human tissue speak only to an association, not a causal relationship. Understanding who with herpes virus, which many of us do, develops AD and who does not may be a critical question for the field to address.
Light and electron micrographs of the assemblies formed by the Aβ and gB peptides. Aβ and gB peptides are shown on the left and right side, respectively: (a and b) light microscopy-phase contrast view, (c and d) thioflavin S staining of the peptides, and (e and f) electron micrographs of negatively stained peptide assemblies.
References:
Cribbs DH, Azizeh BY, Cotman CW, LaFerla FM. Fibril formation and neurotoxicity by a herpes simplex virus glycoprotein B fragment with homology to the Alzheimer's A beta peptide. Biochemistry. 2000 May 23;39(20):5988-94.
Readhead B, Haure-Mirande JV, Funk CC, Richards MA, Shannon P, Haroutunian V, Sano M, Liang WS, Beckmann ND, Price ND, Reiman EM, Schadt EE, Ehrlich ME, Gandy S, Dudley JT. Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron 99, 1–19 July 11, 2018
Eimer, William A. and Vijaya Kumar, Deepak Kumar and Shanmugam, Nanda Kumar N. and Washicosky, Kevin J. and Rodriguez, Alex S. and György, Bence and Breakefield, Xandra O. and Tanzi, Rudolph E. and Moir, Robert D., Alzheimer’s Disease-Associated β-amyloid Is Rapidly Seeded by herpesviridae to Protect Against Brain Infection (2018). Available at SSRN: https://ssrn.com/abstract=3155923 or http://dx.doi.org/10.2139/ssrn.3155923
