Affiliations: [a] Centro de Biología Molecular Severo Ochoa, Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain | [b] Consejo Superior de Investigaciones Científicas (CBM-UAM-CSIC), Cantoblanco, Madrid, Spain | [c] BioPharma Division, Neuron Bio, Parque Tecnológico de Ciencias de la Salud, Edificio BIC, Armilla, Granada, Spain
Correspondence:
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Correspondence to: Javier S. Burgos, Neuron Bio, Parque Tecnológico de Ciencias de la Salud, Edificio BIC, Avda. de la Innovación 1, 18100 Armilla, Granada, Spain. Tel.: +34 958 750 598; Fax: +34 958 750 459; E-mail: [email protected].
Note: [1] Present address: BioPharma Division, Neuron Bio, Parque Tecnológico de Ciencias de la Salud, Edificio BIC, Armilla, Granada, Spain.
Abstract: To date, the main advances in understanding Alzheimer's disease (AD) have revolved around the genetic variants associated with the familial form of the disease, yet the majority of cases are sporadic. The main risk factor for AD is aging, followed by production of the E4 isoform of apolipoprotein E (APOE). Female gender also increases the risk of developing AD. Herpes simplex virus type 1 (HSV-1) has been epidemiologically and experimentally associated with AD, although no studies on its effects over aging have been undertaken. To assess the potential aging-related consequences of HSV-1 brain infection, 2 month-old wild-type and apoE-deficient mice were infected with the virus, and over the next 16 months analyses made of cerebral viral load, neuropathological, morphological, and metabolic changes in the brain, and cognitive performance. Viral load in the central nervous system (CNS) increased with age. The viral load in the brains of aged apoE+/+ female mice was 43 times that seen in apoE−/− male mice. No MRI-detectable morphological differences nor any clear neuropathological differences were seen between 18 month-old infected and mock-infected mice, although differences were seen in younger animals. Neuroinfection was associated with memory deficit and a reduction in metabolic indicators of CNS health.
Keywords: Aging, apolipoprotein E, brain, HSV-1 infection, gender, mouse, MRI
