Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases

Garth L. Nicolson, PhD


Lab Med. 2008;39(5):291-299. 

In This Article

Abstract and Introduction

Often, patients with neurodegenerative or neurobehavioral diseases have chronic, neuropathic infections that could be important in disease inception, disease progression, or increasing the types or severities of signs and symptoms. Although controversial, the majority of patients with various neurodegenerative or neurobehavioral conditions, such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and autistic spectrum disorders, show evidence of central nervous system or systemic bacterial and viral infections. For example, using serology or polymerase chain reaction evidence of Chlamydia pneumoniae, Borrelia burgdorferi, Mycoplasma species, human herpesvirus-1 and -6, and other bacterial and viral infections revealed high infection rates that were not found in control subjects. Although chronic infections were not found in some studies, and the specific role of chronic infections in neurological disease pathogenesis has not been determined or is inconclusive, the data suggest that chronic bacterial or viral infections could be common features of progressive neurodegenerative and neurobehavioral diseases.

Neurodegenerative diseases are chronic degenerative diseases of the central nervous system (CNS) that cause dementia. For the most part, the causes of these brain diseases remain largely unknown.[1] They are characterized by molecular and genetic changes in nerve cells that result in nerve cell degeneration and ultimately nerve dysfunction and death, resulting in neurological signs and symptoms and dementia.[1,2] In addition to neurodegenerative diseases, there are also neurobehavioral diseases that mainly, but not exclusively, appear in the young, such as autistic spectrum disorders (ASD) that encompass autism, attention deficit disorder, Asperger's syndrome, and other disorders.[3]

There appear to be genetic links to neurodegenerative and neurobehavioral diseases, but the genetic changes that occur and the changes in gene expression that have been found in these diseases are complex and not directly related to simple genetic alterations.1,4 In addition, it is thought that nutritional deficiencies, environmental toxins, heavy metals, chronic bacterial and viral infections, autoimmune immunological responses, vascular diseases, head trauma and accumulation of fluid in the brain, changes in neurotransmitter concentrations, among others, are involved in the pathogenesis of various neurodegenerative and neurobehavioral diseases.[1,2,3,5,6,7,8] One of the biochemical changes found in essentially all neurological, neurodegenerative, and neurobehavioral diseases is the overexpression of oxidative free radical compounds (oxidative stress) that cause lipid, protein, and genetic structural changes.[5,6,7,8,9]

Oxidative stress can be caused by a variety of environmental toxic insults, and when combined with genetic factors, pathogenic processes could result.[10] An attractive hypothesis for the causation or promotion of neurological disease involves chronic bacterial or viral toxic products, which result in the presence of excess reactive oxygen species and culminate in pathologic changes.[11,12]

Infectious agents may enter the CNS within infected migratory macrophages, they may gain access by transcytosis across the blood-brain barrier, or enter by intraneuronal transfer from peripheral nerves.[11] Cell-wall-deficient bacteria, principally species of Chlamydia (Chlamydophila), Borrelia, Brucella (among others), bacteria without cell walls, such as Mycoplasma species, and various viruses are candidate infectious agents that may play important roles in neurodegenerative and neurobehavoral diseases.[12,13,14] Since they are usually systemic, such infections can affect the immune system and other organ systems, resulting in a variety of systemic signs and symptoms.[15,16,17,18]


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