In summary, we propose that infectious agents, including HSV1, Chlamydia pneumonia, and spirochetes, reach the CNS and remain there in latent form. These agents can undergo reactivation in the brain during aging, as the immune system declines, and during different types of stress (which similarly reactivate HSV1 in the periphery). The consequent neuronal damage— caused by direct viral action and by virus-induced inflammation— occurs recurrently, leading to (or acting as a cofactor for) progressive synaptic dysfunction, neuronal loss, and ultimately AD. Such damage includes the induction of Aβ which, initially, appears to be only a defense mechanism.
AD causes great emotional and physical harm to sufferers and their carers, as well as having enormously damaging economic consequences. Given the failure of the 413 trials of other types of therapy for AD carried out in the period 2002–2012 , antiviral/antimicrobial treatment of AD patients, notably those who are APOE ɛ4 carriers, could rectify the ‘no drug works’ impasse. We propose that further research on the role of infectious agents in AD causation, including prospective trials of antimicrobial therapy, is now justified.