Journal of Alzheimer's Disease - Volume 2, issue 3-4

Authors: Lerner, Alan J. | Elston, Robert C. | Chen, Chien Hsiun | Friedland, Robert P.

Article Type: Research Article

Abstract: To assess lumbar puncture (LP) stress as measured by Hypothalamic-Pituitary-Adrenal axis response, serum cortisols were measured before and after LP in Alzheimer's disease (AD) and healthy elderly individuals. There were no differences in baseline serum cortisol. AD group had significantly higher cortisols at 165 minutes post-LP. Growth curve analysis confirmed these findings and showed significant differences in cortisol levels overall. The AD males had higher cortisols at 105 minutes post-LP, but no other consistent gender differences emerged. The findings are consistent with the relative reduction in HPA negative feedback seen in AD. Overall, LP induces little change in group mean …cortisol levels relative to inter-individual variation, indicating that while LP is an interesting model of neuroendocrine challenge, it needs to be tested in larger populations. Show more

Keywords: lumbar puncture, stress, Alzheimer's disease, cortisol, hypothalamic-pituitary-adrenal axis

DOI: 10.3233/JAD-2000-23-401

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 193-198, 2000

Authors: Hesse, Camilla | Rosengren, Lars | Vanmechelen, Eugeen | Vanderstichele, Hugo | Jensen, Christer | Davidsson, Pia | Blennow, Kaj

Article Type: Research Article

Abstract: Potential cerebrospinal fluid (CSF) markers for Alzheimer's disease (AD) include tau protein, the 42 amino-acid form of amyloid ß (amyloid ß(1-42)) and apolipoprotein E (apoE). To study new aspects of these protein markers, we examined consecutive CSF samples from 26 patients with acute ischemic stroke. CSF samples were taken on day 0–1, day 2–3, day 7–9, 3 weeks and 3–5 months after the stroke. CSF-tau showed a marked increase day 2–3, which peaked after 1 week and returned to normal after 3–5 months. CSF-tau also showed correlation (r = 0.95; p < 0.01) with the size of the infarct. In contrast, CSF-amyloid ß(1-42) and …CSF-apoE showed no significant changes during the period. The marked increase in CSF-tau levels after acute ischemic stroke indicate that CSF-tau reflect the degree of neuronal damage. The reason for unchanged levels of CSF-amyloid ß(1-42) and CSF-apoE after ischemic stroke remains unclear. Show more

Keywords: apolipoprotein E, amyloid ß(1-42), tau, cerebrospinal fluid (CSF), stroke, cerebral infarction, Alzheimer's disease

DOI: 10.3233/JAD-2000-23-402

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 199-206, 2000

Authors: Grant, Susan M. | Ducatenzeiler, Adriana | Szyf, Moshe | Cuello, A. Claudio

Article Type: Research Article

Abstract: Processing of the amyloid ß-protein precursor is believed to play a critical role in the development of Alzheimer's disease neuropathology. The localization of the human Aß epitope within mature neuroectodermally differentiated embryonal carcinoma (P19) cells, stably transfected with the cDNA coding for a wild form human amyloid ß-protein precursor (AßPP 751) was investigated. For this, we applied high resolution electron microscopy and immunocytochemistry with a newly developed, highly specfic monoclonal antibody (McSA1). We observed immunoreactive signals in a number of subcellular organelles such as early endosomes, the trans-Golgi network and in the dilated rough endoplasmic reticulum, but not in lysosomes. …Occasionally Aß immunoreactivity was associated with microtubules and filaments, with the outer mitochondrial membrane, and with the nuclear envelope. These observations expand on current data regarding intracellular trafficking of AßPP fragments and provoke further questions regarding the role of intracellular Aß peptides in basal conditions and pathological states. Show more

DOI: 10.3233/JAD-2000-23-403

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 207-222, 2000

Authors: Cruz-Sánchez, Félix F. | Durany, Nuria | Thome, Johannes | Riederer, Peter | Zambón, Daniel

Article Type: Research Article

Abstract: Alzheimer's disease (AD) and small vessel disease dementia (SVDD) are common causes of dementia. The ApoE genotype has been proposed as a risk factor for AD. The frequency of the three ApoE alleles was correlated with the neuropathological changes of AD (senile plaques, neurofibrillary tangles and amyloid angiopathy) and SVDD (status lacunaris, status cribosus, leucoencephalopathy, micronecrosis and vascular fibrohyalinosis) in order to validate previous ApoE genotyping results in AD and to identify pre-clinical AD. Representative cerebral regions (cortex, gyrus cinguli, putamen, hippocampus, white matter) from 28 AD cases, 7 SVDD and 38 non-neurological controls were studied using classical histological techniques …and immunohistochemistry for tau protein and amyloid-ß. The frequency of the ApoE allele 4 was significantly increased not only in AD patients but also in aged controls. However, following a detailed histopathological examination was found 62% of this group to exhibit histological changes associated with AD in limited brain areas (entorhinal region, hippocampus and adjacent temporal cortex or entorhinal region and hippocampus, or only in the entorhinal region), but 87% of these cases were found to be ApoE4 positive. The significant differences found in the distribution of ApoE allele frequencies were more marked when these cases were excluded from the control group and included as AD cases. In contrast, the frequency of the ApoE allele 2 is significantly increased in SVDD patients. Using histological techniques we confirmed the clinical diagnoses of all cases and classified the AD patients according to the severity of cortical pathology related to AD, while re-grouping from the control group those cases which had no clinical history of the disease but exhibited typical AD and SVDD histological lessions which could be considered as “pre-clinical” forms of these diseases. Show more

Keywords: Alzheimer's disease, small-vessel disease dementia, polymorphism, genetics, aging, neuropathology

DOI: 10.3233/JAD-2000-23-404

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 223-229, 2000

Authors: Sabbagh, Marwan N. | Galasko, Douglas | Koo, Edward | Thal, Leon J.

Article Type: Research Article

Abstract: Proposed treatments of Alzheimer's disease (AD) are most likely to succeed if they are based on an understanding of the complex biology of AD and its effects on cognition. Treatments may target a single or multiple components of the complex pathology of AD with the hope that by affecting an individual component of AD pathology, the disease course can be affected. One such component is amyloid-ß (Aß), a feature of the senile plaque. Aß may be critical for inducing the pathology seen in AD. Accumulation of Aß may result in a cascade of biochemical events leading to neuronal dysfunction, …which may present opportunities for intervention at multiple different points to slow disease progression. Treatment may be directed towards decreasing Aß production, increasing Aß removal, and decreasing Aß aggregation. Alternatively, treatment may be directed at more distal pathways by: modulating downstream events possibly due to Aß such as free radical toxicity, decreasing inflammation, preventing cell membrane damage, restoring calcium homeostasis, preventing excitotoxicity, and blocking the cellular response to injury by inhibiting neuronal apoptosis. This review underscores the complex biology of Aß specifically looking at the potential targets of therapeutics based on emerging knowledge of this biology. Show more

DOI: 10.3233/JAD-2000-23-405

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 231-259, 2000

Authors: de la Monte, S.M. | Ganju, N. | Feroz, N. | Luong, T. | Banerjee, K. | Cannon, J. | Wands, J.R.

Article Type: Research Article

Abstract: Cell loss and neuritic/cytoskeletal lesions represent two of the major categories of dementia-associated structural abnormalities in Alzheimer's disease (AD). Cell loss is ultimately mediated by apoptosis and mitochondrial DNA damage due to enhanced sensitivity to oxidative stress, but the mechanism responsible for the neuritic/cytoskeletal lesions including the abnormal proliferation of cortical neurites is not known. This study examines the potential role of oxygen free radical injury as a factor contributing to both cell death and neuritic sprouting cascades in AD. PNET2 human neuronal cells were treated with H2 O2 (8 μM to 88 μM) for 24 hours and then …analyzed for viability, DNA damage, and pro-apoptosis, survival, and sprouting gene expression and signaling. H2 O2 -treatment resulted in dose-dependent increases in cell death due to genomic and mitochondrial DNA damage associated with increased levels of 8-OHdG and the p53 and CD95 pro-apoptosis genes, reduced levels of the Bcl-2 survival gene, activation of JNK and p38 stress kinases, and inhibition of PI3 kinase survival signaling. However, the H2 O2 -treated cells also manifested increased expression of growth and sprouting molecules, including GAP-43, nitric oxide synthase 3, neuronal thread protein (NTP; ~ 17 kD and ~ 21 kD forms), proliferating cell nuclear antigen, and phospho-Erk MAPK, and normal levels of the AD-associated ~ 41 kD NTP species, cyclin dependent kinase 5 (cdk-5), and phospho-tau. In addition, the H2 O2 -treated cells had increased levels of p25, the catalytically active and stable cleavage product of p35, which regulates cdk-5 activity. Previous studies demonstrated p25 accumulation in AD brains and p25-induced hyperphosphorylation of tau and neuronal apoptosis. The findings herein suggest that oxygen free radical injury in human CNS neuronal cells is sufficient to cause some but not all of the pro-death and pro-sprouting molecular abnormalities that occur in AD. Show more

Keywords: free radical, apoptosis, mitochondria, neuritic sprouting, neurodegeneration

DOI: 10.3233/JAD-2000-23-406

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 261-281, 2000

Authors: Atwood, Craig S.

Article Type: Research Article

DOI: 10.3233/JAD-2000-23-407

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 283-287, 2000

Authors: Passer, Brent | Pellegrini, Luca | Russo, Claudio | Siegel, Richard M. | Lenardo, Michael J. | Schettini, Gennaro | Bachmann, Martin | Tabaton, Massimo | D'Adamio, Luciano

Article Type: Research Article

Abstract: The amyloid ß protein precursor (AßPP) is sequentially processed by ß- and γ-secretases to generate the Aß peptide. The biochemical path leading to Aß formation has been extensively studied since extracellular aggregates of amyloidogenic forms of Aß peptide (Aß42) are considered the culprit of Alzheimer's disease. Aside from its pathological relevance, the biological role of AßPP proteolysis is unknown. Although never previously described, cleavage of AßPP by γ-secretase should release, together with Aß, a COOH-terminal AßPP Intracellular Domain, herein termed AID. We have now identified AID-like peptides in brain tissue of normal control and patients with sporadic Alzheimer's disease and …demonstrate that AID acts as a positive regulator of apoptosis. Thus, overproduction of AID may add to the toxic effect of Aß42 aggregates and further accelerate neurodegeneration. Show more

DOI: 10.3233/JAD-2000-23-408

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 289-301, 2000

Article Type: Book Review

DOI: 10.3233/JAD-2000-23-409

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 303-304, 2000

Article Type: Abstract

DOI: 10.3233/JAD-2000-23-410

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 305-385, 2000

Article Type: Other

DOI: 10.3233/JAD-2000-23-411

Citation: Journal of Alzheimer's Disease, vol. 2, no. 3-4, pp. 387-387, 2000