Alzheimer's disease and multiple sclerosis: a possible connection through the viral demyelinating neurodegenerative trigger (vDENT)

Alzheimer's disease (AD) and multiple sclerosis (MS) are two CNS disorders affecting millions of people, for which no cure is available. AD is usually diagnosed in individuals age 65 and older and manifests with accumulation of beta amyloid in the brain. MS, a demyelinating disorder, is most commonly diagnosed in its relapsing-remitting (RRMS) form in young adults (age 20-40). The lack of success in a number of recent clinical trials of immune- or amyloid-targeting therapeutics emphasizes our incomplete understanding of their etiology and pathogenesis. Evidence is accumulating that infectious agents such as viruses may contribute either directly or indirectly. With the emerging recognition that demyelination plays a role in risk and progression of AD, we propose that MS and AD are connected by sharing a common environmental factor (a viral infection such as HSV-1) and pathology (demyelination). In the viral DEmyelinating Neurodegenerative Trigger (vDENT) model of AD and MS, the initial demyelinating viral (e.g., HSV-1) infection provokes the first episode of demyelination that occurs early in life, with subsequent virus reactivations/demyelination and associated immune/inflammatory attacks resulting in RRMS. The accumulating damage and/or virus progression deeper into CNS leads to amyloid dysfunction, which, combined with the inherent age-related defects in remyelination, propensity for autoimmunity, and increased blood-brain barrier permeability, leads to the development of AD dementia later in life. Preventing or diminishing vDENT event(s) early in life, thus, may have a dual benefit of slowing down the progression of MS and reducing incidence of AD at an older age.

Automated summary

Alzheimer's disease (AD) and multiple sclerosis (MS) are two CNS disorders with no cure, and recent trials have failed to find effective treatments. Evidence suggests that viral infections, such as HSV-1, may play a role in the development of both diseases. The vDENT model proposes that an initial demyelinating viral infection triggers MS in early life, with subsequent episodes of demyelination and inflammation leading to the development of AD later in life. Preventing or reducing vDENT events early in life could potentially slow down the progression of MS and decrease the incidence of AD.