chapter  11
12 Pages

Down’s Syndrome, Alzheimer’s Disease, and Dementia

ByDavid J. Loren, David M. Holtzman

Down’s syndrome (DS) is one of the oldest known human malformation syndromes; paintings

dating back to the sixteenth century have been found that suggest depictions of individuals with

phenotypic features of DS. The pattern of malformation was formally recognized during a lecture

given in 1846 by Edouard Seguin. The syndrome’s namesake, Dr. John Langdon Down, described

this congenital syndrome characterized by stereotypic facial and cognitive features for the first time

in the medical literature in 1866 (1,2). Although advanced maternal age was understood to be a risk

factor for DS, trisomy 21 as the cause of DS was not appreciated until 1959 when Lejeune

confirmed the presence of three copies of human chromosome 21 in nine infants with DS (3). In

1948, Jervis reported finding neuropathologic features of Alzheimer’s disease [AD, originally

described by Alzheimer in 1907 (4)] in three adults with DS at 35, 42, and 47 years of age (5). DS is

one of the most common human genetic disorders with a prevalence of approximately 1 in 700

births (including live and still births) (6).