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Neurosci Biobehav Rev. 2016 Sep;68:547-562. doi: 10.1016/j.neubiorev.2016.06.014. Epub 2016 Jun 18.

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

Author information

1
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimaraes, Portugal.
2
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimaraes, Portugal. Electronic address: fmarques@ecsaude.uminho.pt.

Abstract

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.

KEYWORDS:

Aging; Alzheimer's disease; Amyloid beta; Blood-brain barrier; Cerebrospinal fluid; Choroid plexus; Cognition; Cytokines; Glial cells; Immune system; Neuroinflammation; Neurons

PMID:
27328788
DOI:
10.1016/j.neubiorev.2016.06.014
[Indexed for MEDLINE]

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