Intranuclear aluminum content in Alzheimer's disease, dialysis encephalopathy, and experimental aluminum encephalopathy

Crapper, D. R.; Quittkat, S.; Krishnan, S. S.; Dalton, Arthur J.; Boni, U. De

doi:10.1007/bf00688530

Cited by 226 publications

(49 citation statements)

References 24 publications

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“…15,[47][48][49][50] Increased aluminum content in the nuclei of AD neurons has been reported and it has been hypothesized in individuals predisposed to AD that aluminum enters neurons more readily, binds to their nuclei and accelerates cell death. 51 A follow-up study of miners subjected to aluminum dust as a putative prevention measure for silicosis in the MacIntyre mines in northern Ontario, has revealed an increased incidence of dementia in the miners so exposed. 52 Furthermore, aluminum levels in the local water supply appear to correlate with the incidence of AD in that location.…”

Section: Exposure To Neurotoxinsmentioning

confidence: 99%

Preventing Dementia

Black

Patterson

Feightner

2001

Can. J. Neurol. Sci.

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Suppl. 1 -S56The concept of primary prevention of dementia is relatively new but will assume increasing importance as dementia prevalence increases in our graying population 1 and as the etiological factors and molecular pathogenetic mechanisms of primary degenerative dementias become better understood. 2Current definitions of dementia require memory impairment and cognitive dysfunction in at least one other domain of sufficient degree to interfere with social functioning.3 In this review we emphasize prevention of dementia in individuals who are cognitively normal but may be at risk for dementia, or who are cognitively impaired but not yet demented. Potential preventative measures include avoidance or control of modifiable risk factors to prevent progression to clinically manifest dementia. Secondary prevention of the degenerative dementias is equivalent to treatment, which is discussed in a companion article in this series. Recent clinical trials have provided evidence for modest symptomatic stabilization with socalled cognitive enhancing agents. If effective retardive therapies or neuroregenerative strategies are developed, in the future it may be possible to delay progression or even partially reverse dementing illness.ABSTRACT: Primary prevention will become increasingly important as dementia prevalence increases and effective retardive therapies are developed. To date, only one randomized controlled trial (involving treatment of systolic hypertension) has demonstrated that the incidence of dementia can be reduced. Physicians should remain alert to possible secondary causes of dementia and correct these whenever possible. Primary and secondary prevention of stroke should reduce dementia related to cerebrovascular disease either directly or as a comorbid factor in Alzheimer's disease (AD). Epidemiological studies have revealed a number of risk factors for AD including genetic mutation, susceptibility genes, positive family history, Down's syndrome, age, sex, years of education, head trauma and neurotoxins. In casecontrol studies non-steroidal anti-inflammatory medication and estrogen replacement therapy appear to decrease the relative risk of developing AD. Further research to develop and test preventative therapies in AD and other dementias should be strongly encouraged.RÉSUMÉ: Prévention de la démence. La prévention primaire va devenir de plus en plus importante à mesure que la prévalence de la démence augmente et que des stratégies efficaces pour en retarder l'apparition sont développées. Pour l'instant, une seule étude randomisée contrôlée (traitement de l'hypertension systolique) a démontré que l'incidence de la démence peut être réduite. Les médecins devraient demeurer vigilants pour détecter la présence causes secondaires de démence et les corriger si possible. La prévention primaire et secondaire de l'accident vasculaire cérébral devrait diminuer l'incidence de la démence reliée à la maladie cérébrovasculaire, soit directement ou comme facteur de comorbidité dans la maladie d'Alzheimer (MA). Des étud...

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Section: Exposure To Neurotoxinsmentioning

confidence: 99%

Preventing Dementia

Black

Patterson

Feightner

2001

Can. J. Neurol. Sci.

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“…The homology of linker histones to nuclear factor 1 (NF 1) suggest that the interaction of these DNA-binding proteins with specific DNA sequences may be a critical factor in the regulation of genetic processes such as transcription [5,6]. TGSDS-PAGE, Tris-glycine-SDS-polyacrylamide gel electrophoresis; PCA, perchloric acid; TAE, Tris-acetate-EDTA; LMG, low mobility group; A, adenine; T, thymine; BRL, Bethesda Research Laboratories Aluminum has been shown to accumulate in Alzheimer affected neocortical nuclei [7], possibly interacting with various components of the nuclear apparatus to disrupt genetic processes [8,9]. The presence of aluminum impairs salt-induced dissociation of linker histones from control nuclei preincubated with aluminum and the elution profile closely resembles that found for nuclei extracted from Alzheimer affected cerebral cortex [I0].…”

Section: Introductionmentioning

confidence: 99%

Linker histone‐DNA complexes: enhanced stability in the presence of aluminum lactate and implications for Alzheimer's disease

1989

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The binding of human brain linker histone proteins to a radiolabelled human Alu repetitive element was examined by mobility shift assay.'Analysis of the complexes formed from protein extracts of whole neocortical nuclei, under physiological conditions in vitro revealed that linker histone H 1 ° has the highest affinity for the Alu DNA sequence. The linker histone-DNA complexes assembled in the presence of aluminum lactate were more resistant to sodium chloride-induced dissociation than those formed in the presence of sodium lactate. The enhanced stability of deoxyribonucleoprotein (DNP) complexes in the presence of the aluminum cation may be of significance in neurodegenerative conditions such as Alzheimer's disease where aluminum preferentially associates with DNA containing structures of the nucleus.

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“…The aluminum hypothesis is controversial (Crapper McLachlan et al 1989, Doll 1993, Nieboer et al 1995): Alzheimer's disease has, though not undisputed (Wood et al 1988, Wettstein et al 1991, Landsberg et al 1992, been associated, on the one hand, with aluminum accumulation in the nuclear chromatin (Crapper et al 1980, Good et al 1992, in the neurofibrillary tangles Brody 1980, Good et al 1992) and focally in specific regions of the brain (Xu et al 1992) and, on the other hand, with aluminum in drinking water (Flaten 1986, Vogt 1986, Martyn et al 1989, Flaten 1990, Frecker 1991, Crapper McLachlan et al 1996.…”

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confidence: 99%