title: [Prenatal infection as driving force of aging-associated neurodegenerative diseases].
abstract: Alzheimer's disease (AD) is the most common type of age-related dementia. Besides few genetic mutations, many non-genetic risk factors are known to significantly influence disease onset and progression. How-ever, the molecular mechanisms and their causal relationships are largely unknown. We developed a mouse model that is characterized by long-term imbalances in inflammatory modulators; achieved through a prenatal infection that constitutes a central aging-relevant factor. This early immune challenge induces a significant acceleration of aging-related neuropathology. Combining the prenatal with a systemic infection during aging, we were able to enhance this pathophysiological effect significantly. Our data imply that prenatal inflammation constitutes a major risk factor of age-related dementia that, in combination with additional immune challenge during aging, is a critical driving force of progressive AD associated neuropathology.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Zürich. knuesel@pharma.uzh.ch
authors.forename: I
authors.initials: I
authors.lastname: Knuesel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000097:blood; D009474:Neurons / Q000276:immunology / Q000473:pathology; D009894:Opportunistic Infections / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000473:pathology; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000473:pathology; D000091042:Reelin Protein; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases