title: Intracerebral propagation of Alzheimer's disease: strengthening evidence of a herpes simplex virus etiology.
abstract: BACKGROUND
  A faulty human protein, abnormally phosphorylated tau, was recently publicized to spread "like a virus" from neuron to neuron in Alzheimer's patients' brains. For several decades, we have been amassing arguments showing that herpes simplex virus type 1 (HSV-1), not p-tau, propagates this interneuronal, transsynaptic pathologic cascade.
  
  
  METHODS
  We reiterate convincing data from our own (and other) laboratories, reviewing the first anatomic foothold neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic immunosurveillance cellularity of the trigeminal ganglia wherein HSV-1 awakens from latency to reactivate; the inabilities of p-tau protein's physical properties to promote it to jump synapses; the amino acid homology between human p-tau and VP22, a key target for phosphorylation by HSV serine/threonine-protein kinase UL13; and the exosomic secretion of HSV-1-infected cells' L-particles, attesting to the cell-to-cell passage of microRNAs of herpesviruses.
  
  
  RESULTS
  The now-maturing construct that reactivated HSV-1 best accounts for the intracerebral propagation of AD changes in the human brain should at last seem highly attractive. This hypothesis might even explain statins' apparent mechanism in some studies for lowering AD incidence.
  
  
  CONCLUSIONS
  Provided that funding agencies will quickly ignite a new realm of investigation, the rejuvenated enthusiasm for testing this optimistic construct holds incalculable potential for rapid, efficacious clinical application, through already available and relatively safe antiviral therapeutics.
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR, USA. ballm@ohsu.edu
authors.forename: Melvyn J
authors.initials: MJ
authors.lastname: Ball
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Lukiw
authors.forename: Eli M
authors.initials: EM
authors.lastname: Kammerman
authors.forename: James M
authors.initials: JM
authors.lastname: Hill
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000821:virology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006561:Herpes Simplex / Q000150:complications*; D006801:Humans; D018139:Simplexvirus; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins