Absence of familial association between dementia of Alzheimer type and down syndrome

Berr, Claudine; Borghi, E.; Rethoré, M O; Lejeune, J; Alpérovitch, A

doi:10.1002/ajmg.1320330427

Cited by 10 publications

(1 citation statement)

References 24 publications

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“…But the gene of the familial form [115] is on chromosome 21; the gene of the precursor of the amyloid substance [11,131] is also on 21 and trisomy 21-affected persons are especially prone to presenile dementia [59,36,52], although there is no excess of Alzheimer disease in their families [9]. Certainly a microscope An enormous number of components: Some 11 billion neurons.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of mental deficiency in trisomy 21

Lejeune

2005

Am. J. Med. Genet.

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~~In trisomy 21, pathogenesis of mental retardation is still poorly understood although the knowledge of the genic content of chromosome 21 is steadily increasing. Short of discovering how to silence selectively one of the 3 chromosomes 21, no rational medication can be envisaged before pathogenesis has been unraveled, at least partially.A biochemical scheme of impairment of mental efficiency is presented. Secondarily, the possible deleterious effects of a given gene overdose are discussed. Cu/Zn SOD, cystathionine beta synthase, S loop protein, phosphofructokinase, purine synthesis and adenosine pharmacology, thyroid disturbance, and elevated TSH with low rT3 as well as biopterine metabolism interferences are reviewed.It is observed that the metabolic paths controlled by these genes, although unrelated at first glance, are in fact tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutually controlled regulation.Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate. From this starting point, systematic research of special sensitivities has begun.Clinical observations and relevant statistical methods allow study of the speed of mental development under various medications. The interest of regulating thyroid metabolism, when needed, is exemplified. Reequilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo-Alzheimer complication is presented.KEY WORDS: mental retardation, methotrexate, monocarbons, thyroid, folic acid, Alzheimer INTRODUCTIONWith upward-slanting eyelids, a little nose in a round face, and incompletely chiseled features, Down syndrome patients look more like children than the usual child does. Every child has short hands with short fingers, but theirs are shorter. All their anatomy is rounded, with no harsh features or stiffness. Their ligaments and muscles have a suppleness producing a tender languor in their posture. This general softness extends even to their character: cheerful and affectionate, they have a special charm easier to cherish than to describe.That is not to say that Down syndrome is a desirable condition. It is a n implacable disorder depriving the children of the most precious quality afforded by our genetic patrimony, the full power of rational thinking.This combination of a tragic chromosomal error with a really attractive nature reveals, in a glimpse, what medicine is all about: to fight against disease and to love the disabled.While pondering over this evening's talk, I suddenly realized that with all the progress accumulated during the last 30 years, the destiny of the trisomy 21-affected persons has not yet been substantially ameliorated.Remarkable achievements in cardiac surgery and in management of infectious or malignant diseases have greatly extended their life expectancy. But a t the same time, early detection and selective abortion have drastically reduced their rate of survival.Looking a t some st...

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