Abstract
Herpes zoster is associated with an increased dementia and neovascular macular degeneration risk and a decline in glycemic control in diabetes mellitus. Because amyloid is present and pathogenic in these diseases, we quantified amyloid, Aβ40, Aβ42, and amylin in 14 zoster and 10 control plasmas. Compared with controls, zoster plasma had significantly elevated amyloid that correlated with Aβ42 and amylin levels and increased amyloid aggregation with addition of exogenous Aβ42 or amylin. These results suggest that zoster plasma contains factor(s) that promotes aggregation of amyloidogenic peptides, potentially contributing to the toxic amyloid burden and explaining accelerated disease progression following zoster.
References
An SSA, Lee BS, Yu JS, Lim K, Kim GJ, Lee R, Kim S, Kang S, Park YH, Wang MJ, Yang YS, Youn YC, Kim S (2017) Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42. Alzheimers Res Ther 17:86–10. https://doi.org/10.1186/s13195-017-0310-6
Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva MJM, Sekijima Y, Sipe JD, Westermark P (2018) Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid 25:215–219. https://doi.org/10.1080/13506129.2018.1549825
Bubak AN, Como CN, Coughlan CM, Johnson NR, Hassell JE Jr, Mescher T, Niemeyer CS, Mahalingam R, Cohrs RJ, Boyd TD, Potter H, Russ H, Nagel MA (2019) Varicella zoster virus infection of primary human spinal astrocytes produces intracellular amylin, amyloid-beta, and an amyloidogenic extracellular environment. J Infect Dis. https://doi.org/10.1093/infdis/jiz560
Chen VC, Wu SI, Huang KY, Yang YH, Kuo TY, Liang HY, Huang KO, Gossop M (2018) Herpes zoster and dementia: a nationwide population-based cohort study. J Clin Psychiatry 79:16m11312. https://doi.org/10.4088/JCP.16m11312
Donath MY, Schumann DM, Faulenbach M, Ellingsgaard H, Perren A, Ehses JA (2008) Islet inflammation in type 2 diabetes: from metabolic stress to therapy. Diabetes Care 31(Suppl 2):S161–S164. https://doi.org/10.2337/dc08-s243
Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE, Selkoe DJ, Guenette S (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A 100:4162–4167
Gershon M, Gershon A (2018) Varicella-zoster virus and the enteric nervous system. J Infect Dis 218(Suppl 2):113–119. https://doi.org/10.1093/infdis/jiy407
Gilden D, Nagel MA, Cohrs RJ, Mahalingam R (2013) The variegate neurological manifestations of varicella zoster virus infection. Curr Neurol Neurosci Rep 13:374. https://doi.org/10.1007/s11910-013-0374-z
Ho JD, Lin HC, Kao LT (2019) Increased risk of neovascular age-related macular degeneration in patients with herpes zoster ophthalmicus: a retrospective cohort study. Acta Ophthalmol 97:e321–e322. https://doi.org/10.1111/aos.13924
Höppener JW, Ahrén B, Lips CJ (2000) Islet amyloid and type 2 diabetes mellitus. N Engl J Med 343:411–419
Jackson K, Barisone GA, Diaz E, Jin LW, DeCarli C, Despa F (2013) Amylin deposition in the brain: a second amyloid in Alzheimer disease? Ann Neurol 74:517–526. https://doi.org/10.1002/ana.23956
Kawai K, Yawn BP (2017) Risk factors for herpes zoster: a systematic review and meta-analysis. Mayo Clin Proc 92:1806–1821. https://doi.org/10.1016/j.mayocp.2017.10.009
Kennedy PG, Grinfeld E, Gow JW (1998) Latent varicella-zoster virus is located predominantly in neurons in human trigeminal ganglia. Proc Natl Acad Sci U S A 95:4658–4662
Kennedy PG, Grinfeld E, Gow JW (1999) Latent varicella-zoster virus in human dorsal root ganglia. Virology 258:451–454
Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J (2006) Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest 116:378–385
Ma J, Yee A, Brewer HB Jr, Das S, Potter H (1994) Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 372:92–94
Mahalingam R, Wellish M, Wolf W, Dueland AN, Cohrs R, Vafai A, Gilden D (1990) Latent varicella-zoster viral DNA in human trigeminal and thoracic ganglia. N Engl J Med 323:627–631
Munoz-Quiles C, Lόpez-Lacort M, Ampudia-Blasco FJ, Diez-Domingo J (2017) Risk and impact of herpes zoster on patients with diabetes: a population-based study, 2009-2014. Hum Vaccin Immunother 13:2606–2611. https://doi.org/10.1080/21645515.2017.1368600
Nagel MA, Rempel A, Huntington J, Kim F, Choe A, Gilden D (2014) Frequency and abundance of alphaherpesvirus DNA in human thoracic sympathetic ganglia. J Virol 88:8189–8192. https://doi.org/10.1128/JVI.01070-14
Schaper NC, Nabuurs-Franssen MH, Huijberts MS (2000) Peripheral vascular disease and type 2 diabetes mellitus. Diabetes Metab Res Rev 16(Suppl 1):S11–S15
Tran TH, Rozenberg F, Cassoux N, Rao NA, LeHoang P, Bodaghi B (2003) Polymerase chain reaction analysis of aqueous humour samples in necrotizing retinitis. Br J Ophthalmol 87:79–83
Tsai MC, Cheng WL, Sheu JJ, Huang CC, Shia BC, Kao LT, Lin HC (2017) Increased risk of dementia following herpes zoster ophthalmicus. PLoS One 12:e0188490. https://doi.org/10.1371/journal.pone.0188490
Wang Z, Ye J, Han YH (2014) Acute pancreatitis associated with herpes zoster: case report and literature review. World J Gastroenterol 20:18053–18056. https://doi.org/10.3748/wjg.v20.i47.18053
Westermark P, Li ZC, Westermark GT, Leckstrom A, Steiner DF (1996) Effects of beta cell granule components on human islet amyloid polypeptide fibril formation. FEBS Lett 379:203–206
Funding
This study was funded by National Institutes of Health (NIH) NIA P01 AG032958, and NIH NINDS R01 NS093716 and R01 NS082228.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bubak, A.N., Beseler, C., Como, C.N. et al. Acute zoster plasma contains elevated amyloid, correlating with Aβ42 and amylin levels, and is amyloidogenic. J. Neurovirol. 26, 422–428 (2020). https://doi.org/10.1007/s13365-020-00830-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13365-020-00830-7