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

Authors: Kawamata, Jun | Shimohama, Shun

Article Type: Research Article

Abstract: Since the loss of cholinergic neurons in the Alzheimer's disease (AD) brain was first reported, considerable evidence in vivo and in vitro has accumulated in support of the cholinergic hypothesis of AD. The hypothesis is greatly supported by the fact that the most promising drugs against AD are inhibitors of acetylcholinesterase (AChE). To identify the possible mutations and/or polymorphisms of neuronal nicotinic acetylcholine receptor (nAChR) genes related to the pathogenesis of sporadic AD, we have performed mutational analyses of the major neuronal nAChR genes (CHRNA3, 4, 7 and CHRNB2) expressed in central nervous system. Allelic analysis showed association …of specific silent or intronic polymorphisms of the CHRNA3 and CHRNA4 genes and AD. Two novel missense point mutations, Ser413Leu in the CHRNA4 gene and Gln397Pro in the CHRNB2 gene, were identified in two different AD cases but were not found in other AD cases and controls. These findings suggested that genetic polymorphisms of the neuronal nAChR genes might be related to the pathogenesis of sporadic AD. Show more

DOI: 10.3233/JAD-2002-4201

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 71-76, 2002

Authors: Lange, Rense | Donathan, Carla L. | Hughes, Larry F.

Article Type: Research Article

Abstract: The strategy of delaying or retarding the progression of Alzheimer's disease requires early diagnosis and treatment. Previous research indicates that measurement of changes in olfaction and cognition will play an important role in the early detection of AD and in the monitoring of therapy effectiveness. Using the data of 177 subjects, our objective was to study the measurement properties of the University of Pennsylvania Smell Identification Test (UPSIT) using a Rasch scaling framework. The results indicate that the UPSIT can yield a linear, unbiased, and unidimensional Rasch measure of human smell recognition abilities. As expected, olfactory recognition ability decreased with …age, and at the rate of about 0.05 Logits per year. Also, Alzheimer's patients showed a decrease in smell recognition equivalent to that experienced by healthy subjects over the course of 30 years. Hormone replacement therapy was not found to affect healthy women's olfactory recognition ability. Additional diagnostic information can be extracted from the analysis of incorrect responses patterns that is relevant to group membership. Show more

Keywords: Alzheimer's disease, UPSIT, Rasch scaling, item bias, distractor analysis

DOI: 10.3233/JAD-2002-4202

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 77-91, 2002

Authors: Meli, M. | Perier, C. | Ferron, C. | Parssegny, F. | Denis, C. | Gonthier, R. | Laurent, B. | Reynaud, E. | Frey, J. | Chamson, A.

Article Type: Research Article

Abstract: Pentosidine, an advanced glycation end product (AGE), was assayed by HPLC in serum proteins from patients with Alzheimer type dementia (AD), patients with diabetes mellitus (D), and healthy (C) age-matched old subjects (mean age from each group = 84 years). Serum pentosidine was significantly different between the three groups despite similar renal function (serum creatinine < 160 μmol/L). In all groups of patients, pentosidine was independent of glycated hemoglobin (HbA1C) and the early glycation marker fructosamine and appeared to be an independent marker, mainly bound to serum albumin. Pentosidine could be an important factor useful for the diagnosis of Alzheimer's …disease. Show more

Keywords: pentosidine, AGE, Alzheimer's disease

DOI: 10.3233/JAD-2002-4203

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 93-96, 2002

Authors: Luo, LuGuang | Yano, Naohiro | Mao, QuanFu | Jackson, I.M.D. | Stopa, E.G.

Article Type: Research Article

Abstract: Thyrotropin-releasing hormone (TRH) is best known for its hypothalamic neuroendocrine role in regulating thyroid function. In extra-hypothalamic regions in vitro , we have shown TRH to have a protective effect against synaptic loss and neuronal apoptosis. A role for TRH in Alzheimer's disease (AD) has not been established previously. In this study, we examined the content of the TRH peptide in the hippocampus of elderly controls (n=5) and AD patients (n=7) by radioimmunoassay (RIA). The TRH concentration was decreased in the AD hippocampus compared to normal elderly controls (p > 0.01). In a separate series of experiments utilizing primary …cell cultures made from rat hippocampus, TRH peptide concentration was depleted by the addition of TRH antiserum. TRH withdrawal was found to enhance the activity of glycogen synthetase kinase-3 (GSK-3β), a critical enzyme necessary for the phosphorylation of tau, as well as the phosphorylation of the tau protein itself. This TRH depletion induced upregulation in phosphorylation that was observed to initiate axonal retraction in cultured neurons. These data suggest that TRH within the hippocampus can regulate the activity of various proteins by phosphorylation/dephosphorylation that may be involved in the pathogenesis of AD. Show more

DOI: 10.3233/JAD-2002-4204

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 97-103, 2002

Authors: Ali-Khan, Zafer

Article Type: Research Article

DOI: 10.3233/JAD-2002-4205

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 105-114, 2002

Authors: Zhang, Shuguang | Janciauskiene, Sabina

Article Type: Research Article

DOI: 10.3233/JAD-2002-4206

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 115-122, 2002

Authors: Nguyen, Kathy Cuc | Rosales, Jesusa L. | Barboza, Milan | Lee, Ki-Young

Article Type: Research Article

DOI: 10.3233/JAD-2002-4207

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 123-126, 2002

Article Type: Book Review

DOI: 10.3233/JAD-2002-4208

Citation: Journal of Alzheimer's Disease, vol. 4, no. 2, pp. 127-128, 2002