| Autor: |
Ferrari RR; Department of Brain and Behavioral Sciences, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy.; Laboratory of Neurobiology and Neurogenetics, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Fantini V; Laboratory of Neurobiology and Neurogenetics, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy.; Laboratory of Translational Research, Azienda USL-IRCCS of Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia, Italy., Garofalo M; Molecular Biology and Transcriptomic Unit, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy., Di Gerlando R; Molecular Biology and Transcriptomic Unit, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy.; Department of Biology and Biotechnology 'L. Spallanzani', University of Pavia, Via Adolfo Ferrata 9, 27100 Pavia, Italy., Dragoni F; Molecular Biology and Transcriptomic Unit, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy., Rizzo B; Molecular Biology and Transcriptomic Unit, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy., Spina E; Laboratory of Neurobiology and Neurogenetics, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Rossi M; Unity of Biostatistics, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Calatozzolo C; Department of Neurology and Neuropathology, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Profka X; Department of Neurology and Neuropathology, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Ceroni M; Department of Neurology and Neuropathology, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Guaita A; Laboratory of Neurobiology and Neurogenetics, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy.; Department of Neurology and Neuropathology, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Davin A; Laboratory of Neurobiology and Neurogenetics, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy., Gagliardi S; Molecular Biology and Transcriptomic Unit, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy., Poloni TE; Department of Neurology and Neuropathology, Golgi Cenci Foundation, Corso San Martino 10, 20081 Abbiategrasso, Italy.; Department of Rehabilitation, ASP Golgi-Redaelli, Piazza E. Samek Lodovici 5, 20081 Abbiategrasso, Italy. |
| Abstrakt: |
Alzheimer's disease (AD) is a neurodegenerative disorder that progressively involves brain regions with an often-predictable pattern. Damage to the brain appears to spread and worsen with time, but the molecular mechanisms underlying the region-specific distribution of AD pathology at different stages of the disease are still under-investigated. In this study, a whole-transcriptome analysis was carried out on brain samples from the hippocampus (HI), temporal and parietal cortices (TC and PC, respectively), cingulate cortex (CG), and substantia nigra (SN) of six subjects with a definite AD diagnosis and three healthy age-matched controls in duplicate. The transcriptomic results showed a greater number of differentially expressed genes (DEGs) in the TC (1571) and CG (1210) and a smaller number of DEGs in the HI (206), PC (109), and SN (60). Furthermore, the GSEA showed a difference between the group of brain areas affected early (HI and TC) and the group of areas that were subsequently involved (PC, CG, and SN). Notably, in the HI and TC, there was a significant downregulation of shared DEGs primarily involved in synaptic transmission, while in the PC, CG, and SN, there was a significant downregulation of genes primarily involved in protein folding and trafficking. The course of AD could follow a definite time- and severity-related pattern that arises from protein misfolding, as observed in the PC, CG, and SN, and leads to synaptic impairment, as observed in the HI and TC. Therefore, a map of the molecular and biological processes involved in AD pathogenesis may be traced. This could aid in the discovery of novel biological targets in order to develop effective and well-timed therapeutic approaches. |
