Intracerebral propagation of Alzheimer's disease: strengthening evidence of a herpes simplex virus etiology.

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.

The high prevalence of herpes simplex virus type 1 DNA in human trigeminal ganglia is not a function of age or gender.

The purpose of this study was to determine the presence and copy numbers of herpes simplex virus type 1 (HSV-1) DNA in human trigeminal ganglia (TG) with respect to age, gender, and postmortem interval (PMI). Human TG (n = 174, obtained from the Oregon Brain Bank, with data on age, gender, and PMI) were analyzed for HSV-1 DNA copies (HSV-1 DNA polymerase gene) by using real-time PCR. We found that 89.

The essential lesion of Alzheimer disease: a surprise in retrospect.

In the absence of any naturally occurring animal model of Alzheimer's disease (AD), the British conviction in the 1970's that clinicopathological investigations of human cases offered the best approach to unraveling the pathogenesis of AD rapidly influenced clinical neuroscientists, neuropathologists and funding agencies in Canada and the USA. But as with my confreres, years of our quantifying AD lesions in autopsy brains have yet to yield definitive conclusions about what is the most important neuronal abnormality. However, during my elusive search, evidence has been slowly gathered that reactivation of latent Herpes simplex virus, traveling from trigeminal ganglia into neighbouring mesial temporal cortex, might best explain the limbic predilection for and earliest site of neurofibrillary tangle formation.

Comparison of clinical and neuropathologic diagnoses of Alzheimer's disease in 3 epidemiologic samples.

Background: Studies of dementia in populations avoid many of the selection biases in clinical samples but require special evaluation and diagnostic methods to obtain high participation rates. To address this issue, we developed a unique in-home dementia assessment. We assessed validity of these assessments using neuropathologic confirmation of the clinical diagnosis in 3 epidemiologic samples.

Statins lower the risk of developing Alzheimer's disease by limiting lipid raft endocytosis and decreasing the neuronal spread of Herpes simplex virus type 1.

Many possible risk factors for Alzheimer's disease (AD) have been investigated, with only a very few showing positive associations and none defining the etiology of the neurodegenerative disease. The presence of herpes simplex virus type 1 (HSV-1) DNA in the brain, coupled with apolipoprotein E allele e4 (ApoE e4), has been suggested to confer an increased risk for AD. Studies have shown that pathogens, including viruses, utilize clathrin-independent endocytosis, i.

Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling.

Alterations in transcription, RNA editing, translation, protein processing, and clearance are a consistent feature of Alzheimer's disease (AD) brain. To extend our initial study (Alzheimer Reports [2000] 3:161-167), RNA samples isolated from control and AD hippocampal cornu ammonis 1 (CA1) were analyzed for 12633 gene and expressed sequence tag (EST) expression levels using DNA microarrays (HG-U95Av2 Genechips; Affymetrix, Santa Clara, CA). Hippocampal CA1 tissues were carefully selected from several hundred potential specimens obtained from domestic and international brain banks.