Alzheimer's disease in Down's syndrome

Abstract

Article abstract-Clinical and neuropathologic evidence points to the development of Alzheimer's disease (AD) in seven Down's syndrome patients above age 40. Dementia was observed in these patients over periods of 2.5 to 9.2 years. The first clinical sign of AD, visual memory loss, was succeeded by impaired learning capacity and decreased occupational and social functioning, and culminated in seizures and urinary incontinence. The morphometric observations of the brains of these seven patients with AD showed that the numbers of plaques and tangles exceeded 20 per 1.5 X 10" pm2 area, in both the prefrontal and hippocampal cortices. Plaques and tangles were also evident in the basal ganglia, thalamus, hypothalamus, and midbrain. In addition, we found that four of the seven brains showed small strokes, and five of the seven amyloid angiopathy. This study also indicates that by longitudinal neuropsychological evaluations and lab tests, which exclude other causes of dementia, the diagnosis of AD can be made even in severely and profoundly retarded patients. NEUROLOGY 1985;35:957-961 Alzheimer's disease in Down's syndrome:Clinicopathologic studies Clinical documentation of AD in DS patients has been made largely by retrospective studies. Moreover, the patients studied who were often institutionalized with profound mental retardation, provided conflicting information in that estimates of AD changes varied from 15%H to 27%" "'to 100%." In a prospective study'j covering 10 years, clinical evidence of AD was seen in 12 of 49 DS patients above age 40 years (24%).We now provide a clinicopathologic description of seven patients with DS with documented clinical manifestations of Alzheimer's dementia extending from 2.5 to 9.2 years before death. Materials and methods. Clinical methods. Cognitivefunctions, defined as learning capacities and memory functions, were assessed quantitatively on a repeated, follow-up basis for five of the seven patients, using methods developed previously.' I I h To minimize the effects of environmental (test) conditions, each patient was examined with the same test materials under conditions as nearly identical as possible in a specially equipped mobile laboratory. T o rule out causes of memory and learning incapacities unrelated to Alzheimer's disease, control studies were performed with different patients and examiners.'4,'A Neurologic examination for focal and frontal release signs were conducted by D.R. Crapper McLachlan. Other clinical data used to estimate "overall regression" were obtained from personal reports by staff and from medical records. Neurologic examinations were conducted on an irregular basis two or three times before death. Cognitive assessments were conducted between two and six times, a t approximately lllr-year intervals.Criteria for inclusion in the study (excluding patient 5) were normal birth record, no prior recorded history of seizures, no gross sensory or motor impairment, and no evidence of focal neurologic signs.Gross and microscopic neuropathologic methods. Each br...

Genetics of Early-Onset Alzheimer Dementia

“…First it was recognized that all aged Down syndrome patients with a complete trisomy 21 developed an ADlike brain pathology [5,6]. As a consequence, linkage analysis with markers on chromosome 21 was performed in LOAD and EOAD families and suggestive linkage to 21q11.2-21q21 was found [7,8].…”

Alternate Aggregation Pathways of the Alzheimer β-Amyloid Peptide

“…Support for this idea comes from studies with Down's syndrome. Patients with this disorder have three copies of chromosome 21 and exhibit extensive A␤ deposition in their brains (14). There appears to be an age-dependent progression from the amorphous A␤ deposits found in the brains of young Down's syndrome subjects to the formation of senile plaques by adulthood (15,16).…”

Chapter 4 Alzheimer's Disease in Adults with Down Syndrome

“…Neuropathology characteristic of some key features of Alzheimer's disease is a virtually universal occurrence in people with Down syndrome over the age of 40 (Mann & Esiri, 1989;Wisniewski, Dalton et al, 1985). In adults with Down syndrome, this pathology is superimposed on a neural substrate already affected by pre-existing developmental abnormalities.…”

“…His interests in the neural underpinnings of behavior led him to develop a brain bank that included over 2,000 cases with their medical and behavioral records. This valuable archive stimulated a widerange of subsequent research, much of which focused on psychological, neuropathological and neurobiological aspects of aging and intellectual disabilities (Barcikowska et al, 1989;Popovitch et al, 1990;Silverman et al, 1993;Wegiel, Wisniewski, Dziewiatkowski, Popovitch, & Tarnawski, 1996), as well as on the linkage between Down syndrome and Alzheimer's disease (Wisniewski, Dalton, McLachlan, Wen, & Wisniewski, 1985;.…”