Journal of Alzheimer's Disease - Volume 11, issue 3

Authors: Raychaudhuri, Mithu | Mukhopadhyay, Debashis

Article Type: Research Article

Abstract: In view of the emerging evidence that amyloid-β load in the brain and neuronal deficits are possibly independent events and the increasing importance of downstream molecular cascades in Alzheimer's Disease (AD) pathogenesis, the role of Amyloid Intracellular C-terminal Domain (AICD) is evaluated. This C-terminal fragment of Amyloid-β protein precursor (AβPP) is cytotoxic and is a major component of AD brain. Different portions of AICD bind to different ‘adaptors’ and are seen to take part in various cellular events including AβPP processing and trafficking, apoptosis, neuronal growth and regulation of gene transcription. Phosphorylation also plays an important role in terms of …choice of binding partners. The review emphasizes the dynamics of the network created by AICD interactions and points to possible alternative routes of AD like neurodegeneration. Show more

Keywords: Amyloid Intracellular C-terminal Domain (AICD), Alzheimer's Disease (AD), Neurodegeneration, Adaptor Proteins, AβPP

DOI: 10.3233/JAD-2007-11311

Citation: Journal of Alzheimer's Disease, vol. 11, no. 3, pp. 343-358, 2007

Authors: Berardi, Nicoletta | Braschi, Chiara | Capsoni, Simona | Cattaneo, Antonino | Maffei, Lamberto

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive memory deficits and cognitive decline. We explored the possibility that Environmental Enrichment (EE) may reduce the disease progression in a comprehensive mouse model for AD like neurodegeneration, the AD11 mice. AD11 mice, which express anti nerve growth factor (NGF) antibodies, develop an age dependent neurodegeneration which encompasses all hallmarks of human AD. We have tested the efficacy of EE starting from 2 months of age, that is before the onset of behavioural deficits in AD11 mice. At 7 months of age, visual recognition memory was tested with …the Object Recognition Test (ORT), spatial memory with the Morris Water Maze (MWM) and the presence of AD pathological hallmarks (Aβ clusters, presence of hyperphosphorylated tau and cholinergic deficit) was assessed immunohistochemically. We found that in AD11 mice exposed to EE from 2 to 7 months of age performance in both memory tests was significantly better than in non EE AD11 mice and indistinguishable from that in wild-type mice of the same age. Exposure to EE from 2 to 7 months significantly reduce the appearance of AD neuropathological hallmarks. A group of AD11 mice was tested also at 12 months of age: we found that 12 months old AD11 mice exposed to EE from 2 to 7 months of age performed significantly better than non EE AD11 mice of the same age and did not differ from 12 months old wt mice. Thus, EE is able to prevent the onset of memory deficits up to at least 12 months of age and to restrain the progression of neurodegeneration in a mouse model of AD. Show more

Keywords: Enriched environment, Alzheimer disease, visual memory, spatial memory, amyloid burden, cholinergic deficit

DOI: 10.3233/JAD-2007-11312

Citation: Journal of Alzheimer's Disease, vol. 11, no. 3, pp. 359-370, 2007

Authors: Woodruff-Pak, Diana S. | Agelan, Alexis | Valle, Luis Del

Article Type: Research Article

Abstract: Supplementing a rabbit's diet with 2% cholesterol alone or with a trace amount of copper created neuropathological changes that resembled those seen in Alzheimer's disease (AD). AD model rabbits were impaired in eyeblink classical conditioning; a form of learning severely impaired in AD. Our aim was to replicate AD rabbit model neuropathology, test eyeblink conditioning in this model, and determine if galantamine (Razadyne™) would ameliorate impaired conditioning. In Experiment 1 rabbit chow with 2% cholesterol and drinking water with 0.12 mg/liter copper sulfate were administered for 10 weeks. Control rabbits received normal food and water. Rabbit brains were probed for …neuropathology. AD model rabbits had significant neuronal loss in frontal cortex, hippocampus and cerebellum. Changes in neurons in the hippocampus were consistent with neurofibrillary degeneration and cytoplasmic immunoreactivity for amyloid-β and tau. In Experiment 2 AD model rabbits were injected daily with vehicle or 3.0 mg/kg galantamine and tested on 750 ms trace and delay eyeblink conditioning. Galantamine improved eyeblink conditioning significantly over vehicle. The AD rabbit model has validity from neuropathological to cognitive levels and offers a promising addition to the available animal models of AD. Galantamine ameliorated impaired eyeblink conditioning, extending the validity of the AD rabbit model to treatment modalities. Show more

Keywords: Eyeblink classical conditioning, trace paradigm, delay paradigm, amyloid-β, tau, neuronal loss, hippocampus, cerebral cortex, cerebellum

DOI: 10.3233/JAD-2007-11313

Citation: Journal of Alzheimer's Disease, vol. 11, no. 3, pp. 371-383, 2007

Authors: Youn, HyeSook | Jeoung, MyoungKun | Koo, YongBum | Ji, Hanlee | Markesbery, William R. | Ji, Inhae | Ji, Tae H.

Article Type: Research Article

Abstract: To identify genes aberrantly expressed in the brain of individuals with Alzheimer's Disease (AD), we analyzed RNA extracts from the hippocampus and cerebellum from 19 AD patients and 15 age- and sex-matched control subjects. Our analysis identified a number of genes that were over-expressed or under-expressed specifically in AD hippocampus. Among these genes, kalirin was the most consistently under-expressed in AD hippocampus, which was verified by semi-quantitative RT-PCR and real time PCR. Kalirin is predominantly expressed in the brain, particularly in the hippocampus, and plays crucial roles in neuronal stability and growth. Our observation is the first to relate kalirin …to AD and a human disease. In addition to kalirin, the genes for voltage-gated Ca++ channel γ subunit 3 and visinin-like protein 1 (a Ca++ sensor protein) were under-expressed, whereas inositol 1,4,5-triphosphate 3-kinase B was over-expressed in AD hippocampus. Collectively, these differential expressions could severely impair calcium homeostasis. Remarkably, these aberrant gene expressions in AD hippocampus were not observed in AD cerebellum. Furthermore, housekeeping genes such as ribosomal protein genes are not affected by AD. These results provide new insights into the biochemistry of AD. Show more

Keywords: Kalirin, Alzheimer's disease, AD, hippocampus, under-expression

DOI: 10.3233/JAD-2007-11314

Citation: Journal of Alzheimer's Disease, vol. 11, no. 3, pp. 385-397, 2007

Article Type: Discussion

DOI: 10.3233/JAD-2007-11315

Citation: Journal of Alzheimer's Disease, vol. 11, no. 3, pp. 399-417, 2007