%0 Journal Article
%T Age-Related Neurodegeneration and Memory Loss in Down Syndrome
%A Jason P. Lockrow
%A Ashley M. Fortress
%A Ann-Charlotte E. Granholm
%J Current Gerontology and Geriatrics Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/463909
%X Down syndrome (DS) is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD) by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS. 1. Introduction The most common cause of dementia is Alzheimer¡¯s disease (AD), with rates of prevalence increasing steadily from 60 years of age to reach almost 40% by the age of 85 [1]. AD is defined as the presence of neuritic plaques, which are composed of extracellular deposits of amyloid beta, and neurofibrillary tangles [2]. Neurodegeneration in the later stages of AD is widespread, with massive synapse loss and an overall decline in grey matter resulting from neuronal loss in cortical and hippocampal regions. Cortical neuronal loss is preceded by degeneration of certain subcortical neuronal populations, including basal forebrain cholinergic neurons (BFCNs) [3] and noradrenergic neurons of the locus coeruleus (LC-NE) [4, 5]. While the majority of AD cases are considered sporadic, mutations in amyloid precursor protein (APP) and presenilins 1 and 2 (PS-1 and PS-2) genes are responsible for most of the cases of AD considered ¡°familial¡± [6]. These mutations lead to alterations in APP metabolism that result in an overabundance of amyloid plaques. Similarly, APP processing is also affected in Down syndrome (DS), a population who exhibit histopathology consistent with AD by the 4th and 5th decades of life with near uniformity, as well as increased risk for dementia [7, 8]. Located on chromosome 21, APP is triplicated in DS, and amyloid-beta deposition is frequently profound in these individuals [9¨C11]. Recently, cases of familial AD resulting from duplication of only the APP locus have been discovered [12], further defining a role for APP in AD dementia. However, few studies have been able to correlate plaque
%U http://www.hindawi.com/journals/cggr/2012/463909/