Genetic, immune and environmental risk factors in Alzheimer's disease

Romagnoli, Martina (2017) Genetic, immune and environmental risk factors in Alzheimer's disease, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia e patologia sperimentale, 29 Ciclo. DOI 10.6092/unibo/amsdottorato/7930.
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Alzheimer's disease (AD) is a complex multi-factorial disease in which several pathogenetic, clinical, environmental and stochastic factors are involved. It is on record that persistent virus infections, the progressive decline of immune competence with ageing and chronic psychological stress exposures might play a pivotal role in AD. This study shows that in patients with clinical and neurological AD diagnosis, antiviral immune response is defective in the majority of AD brain samples. Moreover, gene variants of APOE and IRF7 strongly affect antiviral gene expression profiles in hippocampus. These findings suggest that brains from AD patients have defective antimicrobial immune defences and individual genetic makeup, such as positivity for the APOE ε4 and IRF7 A alleles, further decreases brain immune efficiency. Chronic stress at different stages of life, including intrauterine life, has a negative impact on AD pathology and prenatal stress (PNS) is an important programming factor in brain development and function. The second part of this thesis shows that experimental animal research has the advantage of enabling strict control of environmental factors, such as PNS exposure, that might have a role in AD-related behaviour and neuropathology. Long-term cognitive consequences of PNS in AD mice and the PNS-early neurobiological effects in wild type animals were investigated. As these, mouse represented a useful model to suggest that PNS affects the onset of AD cognitive deficit in a sex-dependent manner and that the impairment of fetal neurodevelopment might influence adult mental health and brain ageing. In conclusion, the presented study gives new perspectives for prevention and treatment of the ageing-associated cognitive decline and AD. Protecting women from chronic stress during pregnancy, on the one side, and maintenance of efficient immune responses during ageing, on the other one, might slowdown neurodegenerative mechanisms associated with senile dementia and positively influence both prevalence and incidence of AD.

Tipologia del documento
Tesi di dottorato
Romagnoli, Martina
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
Alzheimer’s disease Neurodegeneration Viral infection Antiviral response gene polymorphism Brain immunity Herpes virus Neuroinflammation cognitive decline Peripheral inflammation Chronic stress Prenatal stress AD mouse model HPA-axis Cognitive impairment Neurodevelopment
Data di discussione
16 Maggio 2017

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