title: Neuroinflammation, immune system and Alzheimer disease: searching for the missing link.
abstract: Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both. Amyloid-β peptides that aggregate extracellularly in the typical neuritic plaques generate a constant inflammatory environment. This causes a prolonged activation of microglial and astroglial cells that potentiate neuronal damage and provoke the alteration of the blood brain barrier (BBB), damaging the permeability of blood vessels. Recent data support the role of the BBB as a link between neuroinflammation, the immune system and AD. Hence, a thorough investigation of the neuroinflammatory and immune system pathways that impact neurodegeneration and novel exciting findings such as microglia-derived microvesicles, inflammasomes and signalosomes will ultimately enhance our understanding of the pathological process. Eventually, we should proceed with caution in defining a causal or consequential role of neuroinflammation in AD, but rather focus on identifying its exact pathological contribution.
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy. fabio.guerriero01@universitadipavia.it.|Azienda di Servizi alla Persona, Istituto di Cura Santa Margherita of Pavia, Pavia, Italy. fabio.guerriero01@universitadipavia.it.
authors.forename: F
authors.initials: F
authors.lastname: Guerriero
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Sgarlata
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Francis
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Maurizi
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Faragli
authors.affiliation: Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, University of Pavia, Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Perna
authors.affiliation: Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, University of Pavia, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rondanelli
authors.affiliation: Azienda di Servizi alla Persona, Istituto di Cura Santa Margherita of Pavia, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rollone
authors.affiliation: Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ricevuti
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007107:Immune System / Q000276:immunology*; D017628:Microglia
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer disease; Blood brain barrier; Derived-microglia microvesicles; Inflammasome; Neuroinflammation; Signalosome