Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease

Donna M. Wilcock

doi:10.1155/2012/170276

Abstract

Down syndrome (DS) is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation in the DS brain and how the genetics of DS may alter this inflammatory response and change the course of disease in the DS brain. The goal of this review is to highlight our current understanding of inflammation in Alzheimer's disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21.

Highlights

Down syndrome (DS) is the most common chromosomal anomaly among live-born infants and is the most frequent genetic cause of mental retardation [1, 2], with an incidence of one per 733 live births in the United States [3]
There are two signature pathological lesions required for diagnosis; neuritic plaques composed of aggregated amyloid-β (Aβ) peptides, and neurofibrillary tangles composed of hyperphosphorylated, aggregated tau protein [7]
In Alzheimer’s disease (AD), microglia expressing some classic activation markers such as MHC-II, CD68, and CD36 are highly localized to the area immediately surrounding an amyloid plaque or neurofibrillary tangle [18]. While this led some to hypothesize that this reaction was contributing to the toxicity of these pathologies, others suggested that the microglia may be performing a beneficial function in removing the abnormal protein deposits from the brain

Summary

Review Article

Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer’s Disease. Down syndrome (DS) is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is noted as causing Alzheimer’s-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer’s disease. The goal of this review is to highlight our current understanding of inflammation in Alzheimer’s disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21

Introduction

Findings

Immune complexes