Journal of Alzheimer's Disease - Volume 3, issue 6

Authors: Perry, George | Kumar, Bethany S. | Smith, Mark A.

Article Type: Editorial

DOI: 10.3233/JAD-2001-3601

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 521-523, 2001

Authors: Dhitavat, Sirikarnt | Rivera, E.R. | Rogers, Eugene | Shea, Thomas B.

Article Type: Research Article

Abstract: Exposure of neurons to amyloid-beta (Abeta) is accompanied by a cascade of oxidative damage that initiates with lipid peroxidation followed by subsequent generation of cytosolic free radicals and reactive oxygen species (ROS). The antioxidant vitamin E has been utilized to counteract Abeta-induced oxidative stress. We considered herein whether or not the lipid-solubility of vitamin E limits its neuroprotection to membrane-related oxidative damage, and renders it relatively ineffective where prior lipid peroxidation has already generated cytosolic free radicals and ROS. To test this possibility, we treated differentiated SH-SY-5Y human neuroblastoma with vitamin E or a cell-permeant antioxidant, N-acetyl cysteine (NAC), simultaneously …with or 15 min after the application of Abeta. Both vitamin E and NAC prevented Abeta-induced ROS generation when applied simultaneously with Abeta, but only NAC prevented Abeta-induced ROS generation when added to cultures that had previously been exposed to Abeta. These results support the hypothesis that vitamin E can quench Abeta-induced lipid peroxidation, but cannot effectively quench ROS generated by prior lipid peroxidation. These findings in cell culture may provide limited insight into why vitamin E is not fully effective against neurodegeneration in AD in clinical settings, since some neuronal populations are likely to already have been compromised by prior Abeta exposure before vitamin E treatment was initiated. Show more

Keywords: amyloid-beta, vitamin E, N-acetyl cysteine, oxidative stress, antioxidant, Alzheimer's disease

DOI: 10.3233/JAD-2001-3602

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 525-529, 2001

Authors: Pandya, Jignesh D. | Dave, Kunjan R. | Katyare, Surendra S.

Article Type: Research Article

Abstract: Long-term exposure to AlCl3 resulted in 57% phospholipid (TPL) content of synaptic plasma membranes from rat brain with significant decrease in the proportion and content of most of the phospholipid classes (32%- decreases was of lesser magnitude for phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The microsomal TPL and cholesterol (CHL) content decreased by 74% composition. However, the contents of all phospholipids decreased uniformly by about 70%. fluidized in Al fed rats. The results suggest that long-term exposure of rats to Al can alter the structure/function of synaptic plasma membranes and microsomes.

DOI: 10.3233/JAD-2001-3603

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 531-539, 2001

Authors: Jansson, Erik T.

Article Type: Research Article

Abstract: The regulatory agencies of the United States and Canada have placed aluminum on priority lists for research designed to fill data gaps relating to neurotoxicity. This is to create a factual basis for the establishment of health standards for drinking water. In this review, we consider evidence for a significant role for aluminum in AD. Aluminum has been implicated as a potential risk factor in Alzheimer's Disease (AD) and for elderly cognitive impairment by epidemiology studies of drinking water and a food study. Most people experience aluminum brain overload in the aging process. Aluminum levels over 20 times higher than …those of a middle-aged group were found in a brain autopsy study of elderly persons, roughly correlating over the age period with densities of senile plaques and neurofibrillary tangles. Persons with AD have been found to experience increased absorption of aluminum and higher blood levels. More controversially, the majority of brain studies also show elevated aluminum levels, though there is disagreement over location of metal buildup. Clinical intervention to lower brain aluminum by chelation has slowed the progression of AD. Show more

DOI: 10.3233/JAD-2001-3604

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 541-549, 2001

Authors: Exley, Christopher

Article Type: Article Commentary

DOI: 10.3233/JAD-2001-3605

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 551-552, 2001

Authors: Polidori, Maria Cristina | Menculini, Giuseppe | Senin, Umberto | Mecocci, Patrizia

Article Type: Review Article

Abstract: Depression and parkinsonism constitute two frequent findings in elderly demented patients. A large body of research, including epidemiological, retrospective, and prospective studies have contributed to the understanding of complex and common situations in the elderly, in which depression, parkinsonian signs, and cognitive impairment coexist. Many aspects regarding the “associated syndromes of dementia”, however, are still object of debate as well as under current active investigation. The recent dramatic aging of the population is leading to an increasing prevalence of neuropsychiatric comorbidities. This is a problem of great clinical and socio-economical interest, because, when present in the same subject, depression, parkinsonism-related …motor impairment and cognitive impairment may not only act additively or synergistically in deteriorating the functional outcome of the patient, but also lead to their institutionalization. We observed that one half of institutionalized subjects in two nursing homes of Central Italy suffer from an associated syndrome dementia / parkinsonism / depression, that these subjects are significantly more dependent than subjects hospitalized for the same reasons, and that their grade of depression or cognitive impairment is independent of which disease is diagnosed first. Depressed mood, memory impairment and motor difficulties, however, are often underestimated in the elderly, being considered as "normal" aspects of the aging process. The aim of this review is to highlight the clinical relevance of the associated syndromes of dementia, in a way that early diagnosis and treatment of these pathologies are attempted. Show more

Keywords: Parkinson's disease, depression, aging, extrapyramidalism

DOI: 10.3233/JAD-2001-3606

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 553-562, 2001

Authors: Lorío, Gretchen | Avila, Jesús | Díaz-Nido, Javier

Article Type: Research Article

Abstract: Accumulation of hyperphosphorylated tau protein and progressive neuronal loss are among the major hallmarks of certain neurodegenerative disorders including Alzheimer's disease. However, the relationship between tau phosphorylation and neuronal cell death remains unclear. Here we have analyzed tau modifications during two forms of neuronal death, apoptosis and necrosis, using primary cultures of cerebellar granule neurons as a simple model system. Induction of neuronal apoptosis by inhibition of phosphatidylinositol 3-kinase results in a rapid increase in the phosphorylation of tau, which is followed by the dephosphorylation and cleavage of the protein. In contrast, necrosis triggered by high salt shock or glutamate …treatment leads to a rapid dephosphorylation and an almost complete proteolysis of tau. These data suggests that a transient tau hyperphosphorylation occurs at an early stage of apoptosis, whereas tau is dephosphorylated and cleaved during the late phase of apoptosis as well as in necrotic neurons. Show more

DOI: 10.3233/JAD-2001-3607

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 563-575, 2001

Authors: Hossain, Shahanara | Alim, Abdul | Takeda, Kazuya | Kaji, Hiroyuki | Shinoda, Tomotaka | Uéda, Kenji

Article Type: Research Article

Abstract: The NAC region of NACP/α-synuclein is a secondary component of Alzheimer's disease amyloid. α-Synuclein is a major component of Lewy bodies, a typical neuropathological feature of Parkinson's disease. However, the physiological role and deposition mechanisms of α-synuclein are unknown. Structural analyses of α-synuclein should provide a better understanding of its biochemical characteristics. We investigated the digestion of α-synuclein withα-chymotrypsin and cathepsin D, which are reported to be involved in amyloidogenesis, under various conditions in vitro. There are many putative cleavage sites for these enzymes in α-synuclein, including in the NAC region. However, most of the predicted sites remained undigested, and …the NAC region was found to be intact even after extensive digestion. This peculiar characteristic of α-synuclein may be relevant to the abnormal deposition of this molecule in α-synuclein-associated neurodegenerative diseases. Show more

DOI: 10.3233/JAD-2001-3608

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 577-584, 2001

Authors: Guo, Zhenchao | Qiu, Chengxuan | Viitanen, Matti | Fastbom, Johan | Winblad, Bengt | Fratiglioni, Laura

Article Type: Research Article

Abstract: A community cohort of 1270 non-demented 75+ years old persons was followed to evaluate the influence of blood pressure on incidence of dementia. Two hundred and eighteen dementia cases were detected during an average of three years of follow-up. Subjects with baseline systolic pressure ≥ 180 mm Hg had an age- and gender-adjusted relative risk (RR) of 1.6 (95% to persons with systolic pressure of 141-160 mm Hg. This association persisted, although not statistically significant, when education, vascular diseases, and antihypertensive drug use were entered in the model (RR = 1.4; 95% systolic pressure were not related to dementia incidence. …However, individuals with a decrease of 5–19 mm Hg and ≥ 20 mm Hg in systolic pressure from baseline to follow-up had a RR of 1.8 (95% 2.6) and 2.5 (95% also found in subjects with diastolic pressure reduction. In conclusion, our findings support an association between high systolic pressure and increased risk of dementia, whereas blood pressure reduction may be secondary to the dementia process itself. Show more

Keywords: aged, blood pressure, dementia, incidence

DOI: 10.3233/JAD-2001-3609

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 585-591, 2001

Authors: Luo, Yuan | Ingram, Vernon M.

Article Type: Research Article

Abstract: Dephosphorylation of PHF-tau was observed in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP)-treated, but not in oligomycin-treated undifferentiated PC12 cells. FCCP depletes ATP levels by uncoupling oxidative phosphorylation and increases cytosolic calcium levels, while oligomycin inhibits the ATP synthase. We also observed inactivation of several myelin basic protein (MBP) kinases in FCCP-treated PC12 cells, using an in-gel kinase assay. In addition, several phosphotyrosine proteins were dephosphorylated following FCCP-treatment. These studies suggest that MBP kinases and tyrosine phosphatase may be regulated by mitochondrial activity and they may regulate the phosphorylation state of tau. Since mitochondrial dysfunction occurs in Alzheimer disease, such changes in …protein phosphorylation may well be relevant to the disease. Show more

DOI: 10.3233/JAD-2001-3610

Citation: Journal of Alzheimer's Disease, vol. 3, no. 6, pp. 593-598, 2001