Alzheimer-Like Cholinergic Deficiency in Down Syndrome

Yates, Celia M.; Simpson, J. A.; Maloney, A. F. J.; Gordon, Alexander; Reid, Ann

doi:10.1016/s0140-6736(80)92137-6

Cited by 182 publications

(70 citation statements)

References 8 publications

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“…However, the consistent findings of abnormalities in brain stem auditory evoked potentials (9,11), failure of growth and maturation in the brain from an early age, with loss of neurons (41,42) and dendrites (37), and damage to the neurotransmitter system (27,43) would provide the anatomic substrate for the autonomic dysfunction occurring at a central, brain stem, site as a result of the genetic disorder. Our findings carry potential clinical implications.…”

Section: Discussionmentioning

confidence: 98%

Altered autonomic cardiac regulation in individuals with Down syndrome

Iellamo

Galante

Legramante

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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We tested the hypothesis that individuals with Down syndrome, but without congenital heart disease, exhibit altered autonomic cardiac regulation. Ten subjects with Down syndrome (DS) and ten genderand age-matched healthy control subjects were studied at rest and during active orthostatism, which induces reciprocal changes in sympathetic and parasympathetic traffic to the heart. Autoregressive power spectral analysis was used to investigate R-R interval variability. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. No significant differences between DS and control subjects were observed in arterial blood pressure at rest or in response to standing. Also, R-R interval did not differ at rest. R-R interval decreased significantly less during standing in DS vs. control subjects. Low-frequency (LFNU) and high-frequency (HFNU) (both expressed in normalized units) components of R-R interval variability did not differ between DS and control subjects at rest. During standing, significant increase in LFNU and decrease in HFNU were observed in control subjects but not in DS subjects. Baroreflex sensitivity (BRS) did not differ between DS and control subjects at rest and underwent significant decrease on going from supine to upright in both groups. However, BRS was greater in DS vs. control subjects during standing. These data indicate that subjects with DS exhibit reduced HR response to orthostatic stress associated with blunted sympathetic activation and vagal withdrawal and with a lesser reduction in BRS in response to active orthostatism. These findings suggest overall impairment in autonomic cardiac regulation in DS and may help to explain the chronotropic incompetence typically reported during exercise in subjects with DS without congenital heart disease. autonomic nervous system; arterial baroreflex; heart rate variability; orthostatic stress

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Section: Discussionmentioning

confidence: 98%

Altered autonomic cardiac regulation in individuals with Down syndrome

Iellamo

Galante

Legramante

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

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“…Several different mutations, particularly in the gene for the amyloid precursor protein (APP) and its associated processing enzymes, presenilins, have been connected to subtypes of familial AD (for review, see, e.g., Price, 1999;Selkoe, 1999). Interestingly, the gene for APP is located on chromosome 21 in humans, and individuals with Down syndrome (DS), who have a partial or complete trisomy of chromosome 21, have been found to develop most pathological markers for AD early in life (Yates et al, 1980;Casanova et al, 1985;Wisniewski et al, 1985;Mann and Esiri, 1989;Sendera et al, 2000; for review, see Head et al, 2001). Because AD families exhibit a higher rate of DS cases and vice versa, it has been postulated that the two diseases are related (see, e.g., Petronis, 1999).…”

Section: Introductionmentioning

confidence: 99%

Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome

et al. 2003

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ABSTRACT:Individuals with Down syndrome (DS) develop the pathological hallmarks of Alzheimer's disease at an early age, later followed by memory decline and dementia. Women with DS are twice as likely to undergo early menopause, and levels of estradiol correlate with onset of cognitive decline in these women. We have demonstrated that a mouse model of DS, mice with segmental trisomy of chromosome 16 (Ts65Dn), develop a significant deficit in both reference and working memory as young adults (6 -10 months of age), coupled with phenotypic loss of cholinergic neurons in the basal forebrain and altered growth factor levels. In the present study we examined cholinergic and dendritic markers in the hippocampal formation and levels of the amyloid precursor protein (APP) in different brain regions of Ts65Dn mice treated with estradiol for 60 days. The density of the dendritic marker Map2 was significantly decreased in the hippocampal formation of middle-aged trisomic mice (9 -15 months old), and the density of cholinergic neurites (acetylcholinesterase [AChE] histochemistry) was also decreased in specific layers of the hippocampus. Treatment with 17␤-estradiol alleviated the decreases in Map2 and AChE staining, but had no effect on full-length APP levels in the hippocampus. In contrast, a main effect of treatment on APP levels in the striatum was noted, with significant elevations observed in controls and trisomics. These findings demonstrate that estrogen can alleviate deficits in cholinergic and dendritic elements in the hippocampal formation and further strengthens the rationale to explore estrogen replacement therapy in women with DS.

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“…Age-related changes in adults with Down's syndrome (DS) have received considerable attention, primarily because of the observation that people with DS develop the neuropathological changes of Alzheimer's disease (AD) in early life and with increasing age (Ball & Nuttall, 1980 ;Liss et al 1980 ;Yates et al 1980 ;Wisniewski et al 1985 ;Mann, 1993). Neuropathological studies have shown that by the age of 30 years, amorphous amyloid deposition will have been present in the brain for some years and plaques and tangles, predominantly in the amygdala, hippocampus and association areas of the frontal, temporal and parietal cortex characteristic of AD, are invariably present (Mann & Esiri, 1989).…”

Section: Introductionmentioning

confidence: 99%