Journal of Alzheimer's Disease - Volume 40, issue 4

Authors: Qiang, Min | Xiao, Rong | Su, Tao | Wu, Bei-Bei | Tong, Zhi-Qian | Liu, Ying | He, Rong-Qiao

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. Increasing evidence suggests that formaldehyde might be one of the various pathological mechanisms involved in the process of AD onset. Here, we use an AD mouse model, senescence accelerated mouse-prone 8 strain (SAMP8), to study the relationship between endogenous formaldehyde and impairment of cognition. The Morris water maze test was used to evaluate the spatial learning and memory ability of 3-month-old SAMP8 mice, and we correlated the results with endogenous formaldehyde concentrations in the brain. To investigate the underlying reasons for formaldehyde elevation in neurodegenerative …diseases, the expression levels of enzymes involved in formaldehyde metabolism were analyzed, including (anabolic) semicarbazide sensitive amine oxidase (SSAO) and (catabolic) alcohol dehydrogenase III (ADH3). When compared with age-matched SAMR1 mice, we found that in 3-month-old SAMP8 mice the capacity for spatial learning and memory was lower, while brain formaldehyde levels were higher. By using real-time PCR, western blotting, enzyme assay, and immunohistochemistry techniques, we discovered that SSAO expression levels were increased, whereas ADH3 exhibited reduced expression levels of mRNA, protein, and enzyme activity. The imbalance of these metabolic enzymes may represent a causal explanation for the observed formaldehyde elevation in the SAMP8 brain. Such increase could be responsible for the observed tau hyperphosphorylation assumed to result in protein aggregation, ultimately leading to cognitive impairment. Taken together, our study gives new insights into the role of metabolic enzymes in age-related accumulation of formaldehyde, and thus the establishment of neurodegenerative diseases. Show more

Keywords: Alzheimer's disease, enzymes, formaldehyde, metabolism, SAMP8, SAMR1, SSAO, ADH3

DOI: 10.3233/JAD-131595

Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 1039-1053, 2014

Authors: Zimmermann, Ruediger | Huber, Ellen | Schamber, Christine | Lelental, Natalia | Mroczko, Barbara | Brandner, Sebastian | Maler, Juan Manuel | Oberstein, Timo | Szmitkowski, Maciej | Rauh, Manfred | Kornhuber, Johannes | Lewczuk, Piotr

Article Type: Research Article

Abstract: Changes in the concentrations of amyloid-β (Aβ) in the body fluids are the earliest alterations observed in Alzheimer's disease (AD), however, there is a lack of data about how early these alterations occur, before the onset of the clinical symptoms. APOE genotype is the most recognized genetic risk/protective factor of AD, meaning that a group of non-demented persons carrying ε4 allele is enriched in the subjects who will develop AD, compared to the group of non-carriers. Therefore, we studied the plasma concentrations of Aβ peptides (Aβ1-42 , Aβ1-40 , Aβx-42 , and Aβx-40 ), and the APOE genotype in 173 …young volunteers (average age, 28 ± 7.6 years) without memory deficits, in order to see whether the non-demented group of subjects at risk already characterize with Aβ changes three-to-four decades before the age at which dementia usually occurs. We did not find statistically significant differences among the groups of ε4 carriers, ε3 homozygotes, and ε2 carriers. We conclude that the APOE genotype does not influence the metabolism of the Aβ peptides in young persons without memory deficits. Show more

Keywords: Amyloid-β, APOE genotype, blood biomarkers, non-demented volunteers

DOI: 10.3233/JAD-132687

Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 1055-1060, 2014

Authors: George, Daniel R. | D'Alton, Simon

Article Type: Review Article

DOI: 10.3233/JAD-140707

Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 1061-1062, 2014

Article Type: Correction

DOI: 10.3233/JAD-149003

Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 1063-1063, 2014

Article Type: Other

DOI: 10.3233/JAD-132688

Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 1065-1067, 2014

Article Type: Other

DOI: 10.3233/JAD-2014-40426

Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 1069-1080, 2014