Abstract
Adults with Down syndrome (DS) have an exceptionally high prevalence of Alzheimer disease (AD), with an earlier age of onset compared with the neurotypical population. In addition to beta amyloid, immunological processes involved in neuroinflammation and in peripheral inflammatory/autoimmune conditions are thought to play important roles in the pathophysiology of AD. Individuals with DS also have a high prevalence of autoimmune/inflammatory conditions which may contribute to an increased risk of early AD onset, but this has not been studied. Given the wide range in the age of AD onset in those with DS, we sought to evaluate the relationship between the presence of inflammatory conditions and the age of AD onset. We performed a retrospective study on 339 adults with DS, 125 who were cognitively stable (CS) and 214 with a diagnosis of AD. Data were available for six autoimmune conditions (alopecia, celiac disease, hypothyroidism, psoriasis, diabetes and vitamin B12 deficiency) and for one inflammatory condition, gout. Gout was associated with a significant delay in the age of AD onset by more than 2.5 years. Our data suggests that inflammatory conditions may play a role in the age of AD onset in DS. Further studies are warranted.
Highlights
IntroductionThe typical age of onset of Alzheimer disease (AD) in people with Down syndrome (DS) is approximately twenty years earlier than in those with sporadic AD [7], there is considerable heterogeneity in the age of onset of AD in DS, with some individuals developing AD at as young as 40 and some after the age of 70 [7]
The cohort consisted of 125 individuals (37%) who were cognitively stable (CS) and 214 individuals (63%) with possible or probable Alzheimer disease (AD)
Our study is the first to analyze the relationship between inflammatory and/or autoimmune medical comorbidities commonly present in Down syndrome (DS) and the age of AD onset
Summary
The typical age of onset of AD in people with DS is approximately twenty years earlier than in those with sporadic AD [7], there is considerable heterogeneity in the age of onset of AD in DS, with some individuals developing AD at as young as 40 and some after the age of 70 [7]. Factors which underlie this considerable variability are still unknown but may provide important insights
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