There is a range of evidence to suggest infection by various fungi, bacteria, and viruses might contribute to the development of Alzheimer's disease (AD), all of this being somewhat unrelated to evidence suggesting that Alzheimer's is a lifestyle disease created by many of the same root causes as type 2 diabetes, such as obesity and lack of exercise. It may yet turn out to be the case that Alzheimer's is better considered as a collection of discrete conditions that happen to have the same end point. In this open access paper researchers look over what is known of the relationship between the ubiquitous persistent herpes simplex virus 1 (HSV-1) and Alzheimer's:
Among the multiple factors concurring to Alzheimer's disease (AD) pathogenesis, greater attention should be devoted to the role played by infectious agents. Growing epidemiological and experimental evidence suggests that recurrent herpes simplex virus type-1 (HSV-1) infection is a risk factor for AD although the underlying molecular and functional mechanisms have not been fully elucidated yet.
Herpes simplex type 1 virus primarily infects epithelial cells of oral and nasal mucosa. The newly produced viral particles may enter sensory neurons and, by axonal transport, reach the trigeminal ganglion where usually establishes a latent infection. The virus undergoes periodic reactivation cycles in which the newly formed viral particles are transported back to the site of primary infection through the sensory neurons, causing the well-known cold sores and blisters. However, the bipolar trigeminal ganglion neurons also project to the trigeminal nuclei located in the brainstem. From here, neurons project to the thalamus to finally reach the sensory cortex. This is the path through which the reactivated virus may reach the central nervous system (CNS), where it may cause acute neurological disorders like encephalitis or a mild, clinically asymptomatic, infection, or establish life-long latent infection. The weakening of immune system occurring during aging may favor this process. In addition to the neuronal route, HSV-1 may enter the CNS through the blood stream. Experimental evidence suggest that accumulation of intracellular damage caused by repeated cycles of viral reactivation may concur to neurodegeneration.
Some reports suggest that during infection herpes virus interacts with several human proteins that it uses to enter the cell and to move from plasma membrane to the nucleus and back. HSV-1 also uses the host's transcriptional machinery to replicate and binds to proteins that control immune surveillance or apoptosis. Noteworthy, in the attempt to eliminate the virus, host may even cause cell damage via immune and inflammatory responses targeting the virus-containing cells. If this happens in the CNS, HSV-1-induced inflammatory response may result in cell death and neurodegeneration.
Epidemiological, immunological and molecular evidence link HSV-1 infections to AD pathogenesis. HSV-1 is a ubiquitous virus that affects more than 80% of people over 65 worldwide. The first evidence suggesting the involvement of HSV-1 in AD dates back to 1982 and is based on the observation that people surviving HSV-1 related encephalitis showed clinical signs reminiscent of AD (i.e., memory loss and cognitive impairment), and that brain regions primarily affected were the same regions compromised in AD. During the last 30 years several research groups have conducted many studies providing solid support to the involvement of HSV-1 infection in AD pathogenesis. Here we will briefly summarize the main results of these researches.