Alzheimer's disease (AD) is a multifactorial disease with genetic (70%) and environmental (30%) causes. Among the genetic factors are genes associated with a family history of the disease (familial AD, FAD) and sporadic AD (SAD). The genes: APP (amyloid precursor protein), PSEN1 (Presenilin 1) and PSEN2 (Presenilin 2) are responsible for the presence of FAD. The APOE gene is responsible for the sporadic form of the disease. Other molecular factors related to the immunological cause (TREM2) of the disease are a disorder of the lipid (ABCA1, ABCA7) or biothiol (MTHFD1) metabolism and of the transport of metabolites (BIN1). Currently, it is believed that APOE is a risk factor for both SAD and late-onset FAD. The pathomechanism of AD is most commonly explained as based on the amyloid cascade theory. This theory is related to the FAD, although there are reports indicating the probability of its occurrence in the SAD. It seems that the excessive deposition of β-amyloid (Aβ) peptides and intracellular neurofibrillary tangles of tau protein hyperphosphorylated forms contribute to the damage of both DNA and RNA. Furthermore, it is believed that RNA-interference can affect both the level of pathological proteins (Aβ, tau protein) and the onset and progress of AD. It seems that a complete understanding of both FAD and SAD pathogenesis may contribute to the search for earlier clinical diagnosis and to an understanding of later occurrence of the disease, which may help modify its course and affect more effective therapy of this incurable neurological disease.

A b s t r a c t Alzheimer's disease (AD) leads to generation of β-amyloid (Aβ) in the brain. Alzheimer's disease model PS/APP

Similarly to Hcy, ADMA seems to be a potential risk factor of AD and important factor for progress of dementia.

Alzheimer's disease (AD) leads to the generation of β-amyloid (Aβ), which may damage DNA and thus lead to apoptosis induction by the p53 pathway. Dysfunction of the p53 protein may then be connected with the development of AD. Studies were conducted on 28 AD patients and 30 non-AD controls. Analysis of TP53 mutations in exon 7 was performed on DNA isolated from whole blood and biochemical parameters in the peripheral lymphocytes of these individuals. Our study showed a silent mutation TP53 C708T (21%) [p < 0.05] and a missense mutation TP53 C748A (4%) only in the AD patients. Moreover, in AD patients with the TP53 C748A mutation, the level of 8-oxo-2'deoxyguanosine (8-oxo2dG) was more than 5 times higher than the average level in this study group. In AD patients with the wild-type TP53 gene, the level of 8-oxo2dG was correlated with the level of protein p53 (R = +0.7388, p < 0.05). The level of the oxoguanine DNA glycosylase 1 (OGG1) protein was similar in AD patients with the silent mutation and the wild-type gene TP53 (p < 0.05) and lower than in the controls. It appears that mutations in exon 7 of TP53 (C748A, C708T) may be associated with pathogenesis of AD.

present even in the pre-plaque stages. Conclusions: Proteomic characterization of the rat model of Alzheimer's disease compared to wild type controls reveals early dysregulation of molecular pathways that are expected to contribute to AD pathology, as well as additional pathways that may represent novel targets for therapeutic intervention. These early changes might well represent preclinical features of the Abeta-driven pathology. Further characterization of this transgenic rat model will include analysis of biomarker profiles.Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes cognitive and behavioral impairment. It is characterized by the accumulation of amyloid plaques and neurofibrillary tangles. Histochemical analyses of AD brain tissue have shown BuChE to be present in ß-amyloid (Aß) plaques and neurofibrillary tangles (NFTs). In addition, it has been found that when BuChE is associated with plaques that they are in a more malignant, ß-pleated, thioflavin-S positive form. It is not clear whether the BuChE associated with Aß plaques is causative of AD, interferes with disease progression or is an epiphenomenon. An animal model that develops similar BuChE-associated Aß plaques, could help elucidate the role of BuChE in this pathology. Methods: The B6.Cg-Tg (APP SWE / PSEN1dE9) 85Dbo/j transgenic mouse was used to determine if BuChE associates with Aß plaques in a mouse model of AD. Four mice, aged 15.5 months, were used in this study. Brain tissue was stained using Aß immunohistochemistry, thioflavin-S and BuChE histochemistry. Plaque loads were quantified using NIH ImageJ software and recorded as a percentage of the total area. Results: We found that this animal model develops Aß and thioflavin-S plaques with BuChE activity (Figure 1). The pathology seen, in terms of morphology, distribution and abundance of Aß, thioflavin-S and BuChE plaques, closely resembled many aspects seen in AD. There was a high correlation in the distribution and abundance of Aß, thioflavin-S and BuChE plaques. Furthermore, based on the percent of area covered by pathology, BuChE staining was less than Aß staining but more than thioflavin-S staining. Ab, thioflavin-S and BuChE plaques were found in cortical and hippocampal areas as well as in olfactory structures, amygdala and the cerebellum. There were few scattered plaques in the thalamus, striatum and certain fibre tracts as well. Conclusions: Based on the work with this APP/PS1 Cg-Tg mouse model, BuChE association with Aß plaques may represent an intermediate stage in the development of malignant, ß-pleated, thioflavin-S positive plaques. Further study with this animal model may help elucidate the role of BuChE in AD pathology. Figure 1. b-amyloid immunohistochemistry, thioflavin-S staining and butyrylcholinesterase histochemistry in a 15.5 month old B6. Cg-Tg (APPSWE/PSEN1dE9) 85Dbo/j mouse. scale bar ¼ 1mm.Background: Alzheimer's disease (AD) is one of the most important neurodegenerative diseases. Mutations in amyloid precursor protein...