Insights on the pathophysiology of Alzheimer's disease: The crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system

• Published in: Neuroscience and biobehavioral reviews 2016-09, Vol.68, p.547-562
• Main Authors: Dá Mesquita, Sandro, Ferreira, Ana Catarina, Sousa, João Carlos, Correia-Neves, Margarida, Sousa, Nuno, Marques, Fernanda
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer Disease; Alzheimer's disease; Amyloid beta; Amyloid beta-Peptides; Blood-brain barrier; Brain; Cerebrospinal fluid; Choroid plexus; Cognition; Cytokines; Glial cells; Humans; Immune System; Neuroinflammation; Neurons
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2016.06.014

•Increased brain amyloid burden and neuroinflammation are central features of AD.•The brain barriers play a role in the inflammatory response in aging and in AD.•All brain parenchymal cell types take part in the neuroinflammatory response in AD.•The peripheral immune system modulates both brain pathology and cognition in AD. Alzheimer's disease (AD) is the most common form of dementia, whose prevalence is growing along with the increased life expectancy. Although the accumulation and deposition of amyloid beta (Aβ) peptides in the brain is viewed as one of the pathological hallmarks of AD and underlies, at least in part, brain cell dysfunction and behavior alterations, the etiology of this neurodegenerative disease is still poorly understood. Noticeably, increased amyloid load is accompanied by marked inflammatory alterations, both at the level of the brain parenchyma and at the barriers of the brain. However, it is debatable whether the neuroinflammation observed in aging and in AD, together with alterations in the peripheral immune system, are responsible for increased amyloidogenesis, decreased clearance of Aβ out of the brain and/or the marked deficits in memory and cognition manifested by AD patients. Herein, we scrutinize some important traits of the pathophysiology of aging and AD, focusing on the interplay between the amyloidogenic pathway, neuroinflammation and the peripheral immune system.