Earlier Age of Onset of Alzheimer's Disease in Patients with Both the Transferrin C2 and Apolipoprotein E‐ɛ4 Alleles

Rensburg, Susan J. van; Potocnik, Felix; Villiers, J. Nico P. de; Kotze, Maritha J.; Taljaard, J. J. F.

doi:10.1111/j.1749-6632.2000.tb06369.x

Cited by 25 publications

(17 citation statements)

References 15 publications

(30 reference statements)

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“…This variant occurs in high frequency in patients with AD compared with non-demented controls [157 -160]. It has also been shown that early onset of AD is observed in patients with both ApoE4 and TfC2 alleles [161]. Further, and that Al uptake occurs more in neurons of cortex and hippocampus, which are rich in Tf receptors [31].…”

Section: Cross-talk Between Genetic Susceptibility and Al In Admentioning

confidence: 99%

Aluminium in Alzheimer?s disease: are we still at a crossroad?

Gupta

Anitha

Hegde

et al. 2005

CMLS, Cell. Mol. Life Sci.

277

147

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Aluminium, an environmentally abundant non-redox trivalent cation has long been implicated in the pathogenesis of Alzheimer's disease (AD). However, the definite mechanism of aluminium toxicity in AD is not known. Evidence suggests that trace metal homeostasis plays a crucial role in the normal functioning of the brain, and any disturbance in it can exacerbate events associated with AD. The present paper reviews the scientific literature linking aluminium with AD. The focus is on aluminium levels in brain, region-specific and subcellular distribution, its relation to neurofibrillary tangles, amyloid beta, and other metals. A detailed mechanism of the role of aluminium in oxidative stress and cell death is highlighted. The importance of complex speciation chemistry of aluminium in relation to biology has been emphasized. The debatable role of aluminium in AD and the cross-talk between aluminium and genetic susceptibility are also discussed. Finally, it is concluded based on extensive literature that the neurotoxic effects of aluminium are beyond any doubt, and aluminium as a factor in AD cannot be discarded. However, whether aluminium is a sole factor in AD and whether it is a factor in all AD cases still needs to be understood.

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Section: Cross-talk Between Genetic Susceptibility and Al In Admentioning

confidence: 99%

Aluminium in Alzheimer?s disease: are we still at a crossroad?

Gupta

Anitha

Hegde

et al. 2005

CMLS, Cell. Mol. Life Sci.

277

147

View full text Add to dashboard Cite

show abstract

“…Of particular interest in this regard was to investigate the potential interactive role between age and the e4-allele, since the negative influences of the e4 allele on olfactory function and dementia prevalence are age-related (Li et al 2002;Olofsson et al in press;van Rensburg et al 2000). Also, given that a range of health conditions may have a negative impact on olfactory and cognitive functions, these factors were statistically controlled for.…”

Section: Introductionmentioning

confidence: 99%

Odor Identification Deficit as a Predictor of Five-Year Global Cognitive Change: Interactive Effects with Age and ApoE-ε4

et al. 2009

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Olfactory impairments are present in common neurodegenerative disorders and predict conversion to dementia in non-demented individuals with cognitive impairment. In cognitively intact elderly, evidence is sparse regarding the role of olfactory deficits in predicting cognitive impairment. The present study investigated predictors of 5-year prospective decline in the Mini-Mental State Examination (MMSE) in a large (n = 501), population-based sample of elderly (65-90 years) individuals. All participants were genotyped for the ApoE gene, assessed for health factors, and were non-demented at the baseline assessment. After partialling out the influences of demographic and health-factors at baseline and dementia at follow-up, poor odor identification ability in combination with older age and the ApoE-epsilon4 allele predicted larger prospective global cognitive decline. This effect could not be produced by a vocabulary test. In sum, the findings suggest that an olfactory deficit can dissociate between benign and malign global cognitive development in non-demented, very old epsilon4-carriers, who are at high risk of developing dementia.

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“…It consists of 679 amino acids folded into two domains, each of which contains a metal ion-binding site. Some studies have indicated that there is a correlation between a genetic variant of Tf, carrying a P570S mutation called TfC2, and AD [71][72][73]. Tf is N-glycosylated at Asn413 and Asn611, and, owing to heterogeneity in the glycan structures, several glycosylation variants exist.…”

Section: Tf and Glycosylationmentioning

confidence: 99%

The role of protein glycosylation in Alzheimer disease

2013

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Glycosylation is one of the most common, and the most complex, forms of post-translational modification of proteins. This review serves to highlight the role of protein glycosylation in Alzheimer disease (AD), a topic that has not been thoroughly investigated, although glycosylation defects have been observed in AD patients. The major pathological hallmarks in AD are neurofibrillary tangles and amyloid plaques. Neurofibrillary tangles are composed of phosphorylated tau, and the plaques are composed of amyloid b-peptide (Ab), which is generated from amyloid precursor protein (APP). Defects in glycosylation of APP, tau and other proteins have been reported in AD. Another interesting observation is that the two proteases required for the generation of amyloid b-peptide (Ab), i.e. c-secretase and b-secretase, also have roles in protein glycosylation. For instance, c-secretase and b-secretase affect the extent of complex N-glycosylation and sialylation of APP, respectively. These processes may be important in AD pathogenesis, as proper intracellular sorting, processing and export of APP are affected by how it is glycosylated. Furthermore, lack of one of the key components of c-secretase, presenilin, leads to defective glycosylation of many additional proteins that are related to AD pathogenesis and/or neuronal function, including nicastrin, reelin, butyrylcholinesterase, cholinesterase, neural cell adhesion molecule, v-ATPase, and tyrosine-related kinase B. Improved understanding of the effects of AD on protein glycosylation, and vice versa, may therefore be important for improving the diagnosis and treatment of AD patients.

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Earlier Age of Onset of Alzheimer's Disease in Patients with Both the Transferrin C2 and Apolipoprotein E‐ɛ4 Alleles

Cited by 25 publications

References 15 publications

Aluminium in Alzheimer?s disease: are we still at a crossroad?

Aluminium in Alzheimer?s disease: are we still at a crossroad?

Odor Identification Deficit as a Predictor of Five-Year Global Cognitive Change: Interactive Effects with Age and ApoE-ε4

The role of protein glycosylation in Alzheimer disease

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