PSYCHIATRIC COMORBIDITIES IN PARKINSON\u27S DISEASE SEEN THROUGH THE PRISM OF GENOMICS AND EPIGENETICS

Parkinson\u27s disease (PD) is a neurodegenerative disorder clinically characterized by motor dysfunctions due to progressive loss of dopaminergic neurons and a broad spectrum of non-motor symptoms. Interestingly, non-motor symptoms like depression, anxiety and psychosis are often present several years before the occurrence of classic motor features seriously affecting patient quality of life. Their presence is often misleading, delaying the correct diagnosis of PD. Despite its high incidence, the pathophysiology and aetiology of neuropsychiatric symptoms associated with PD remains unclear. Currently, a lot of interest lays in research looking for genetic predictors of motor and non-motor symptoms in PD. The availability of next-generation sequencing technology for genome, epigenetic and transcriptional analysis opens the door to a new way of studying multifactorial diseases like PD and their comorbidities. In this review we will present new insights in the genomic and epigenetic background of psychiatric comorbidity in Parkinson\u27s disease

Early Diagnosis of Alzheimer’s Disease

Alzheimerova bolest progresivna je degenerativna bolest središnjega živčanog sustava i najčešći uzrok demencije u osoba starijih od 65 godina, a ujedno i najčešća neurodegenerativna bolest. Karakterizirana je ekstracelularnim nakupljanjem β-amiloida u mozgu, kao i nakupljanjem neurofibrilarnih snopića u neuronima. Biokemijski procesi koji su uključeni u razvoj Alzheimerove bolesti na kraju dovode do raširene stanične smrti i gubitka neurona apoptozom. Moderna klinička obrada bolesnika s Alzheimerovom bolesti znatno je unaprijedila mogućnost pravodobnog postavljanja dijagnoze. Klinička obrada uključuje niz kliničkih i dijagnostičkih postupaka poput strukturnih, funkcionalnih i molekularnih neuroslikovnih metoda te neurokognitivnog testiranja, neurofizioloških metoda, genske analize ili određivanja biomarkera iz cerebrospinalnog likvora. Premda je donedavno vrijedilo pravilo da se dijagnoza Alzheimerove bolesti može postaviti samo post mortem, današnje dijagnostičke smjernice omogućavaju postavljanje dijagnoze u bolesnika sa specifičnošću i senzitivnošću višima od 90%. Napredak u dijagnostičkim algoritmima također je omogućio rano postavljanje dijagnoze, što uvelike pomaže pri daljnjem razvoju neuroprotektivne terapije i njezinu pravodobnom davanju.Alzheimer’s disease is a progressive degenerative disorder of the central nervous system, and the most common cause of dementia in people over 65 years of age, as well as the most common neurodegenerative disease. Alzheimer’s disease is characterized by the extracellular accumulation of β-amyloid in the brain, as well as the accumulation of neurofibrillary tangles in neurons. Biochemical processes involved in the development of Alzheimer’s disease ultimately lead to widespread cell death and neuronal loss through apoptosis. Modern clinical work-up of patients with Alzheimer’s disease significantly improved the possibility of timely diagnosis. Clinical work-up includes a whole range of clinical and diagnostic procedures such as structural, functional and molecular neuroimaging, neurocognitive testing, neurophysiological methods, genetic analysis and cerebrospinal fluid biomarkers. Despite the previous understanding that the diagnosis of Alzheimer’s disease can only be made by a postmortem examination, today’s diagnostic guidelines allow the diagnosis with specificity and sensitivity of more than 90%. The aforementioned progress in diagnostic algorithms also enabled early diagnosis thus allowing the development and timely administration of neuroprotective therapies

Analiza ekspresije gena u koštanom tkivu osteoporotičnih miševa

Ovaricetomized (OVX) animals represent an optimal model to investigate bone loss in osteoporosis. To further elucidate the underlying mechanisms of decreased bone formation and increased bone resorption following OVX, we conducted gene expression profiling experiments using bone samples of ovariectomized C57BL/6J mice. Following OVX, genes involved in immune response, cell cycle regulation, growth, apoptosis and bone resorption were upregulated, while genes that are important for regular cell processes, mitosis, metabolism of carbohydrates, extracellular matrix structure, angiogenesis, skeletal development and morphogenesis were downregulated. Among bone specific genes we observed upregulation of interleukin 7 (IL-7), IL-7 receptor and matrix metallopeptidase 8, while genes such as transforming growth factor-beta 3, procollagen type I and procollagen type VI exhibited marked decrease in expression. We also observed downregulation of two genes, parathyroid hormone receptor 1 and WD repeat domain 5, that are involved in skeletal development but were not previously reported to be altered in osteoporosis. We further performed gene set enrichment analysis (GSEA) in order to calculate enrichment of pathways specifically altered in murine bones following ovariectomy. In conclusion, OVX greatly influences expression of various genes involved in diverse biological processes confirming the notion that numerous pathways play an important role in pathophysiology of osteoporosis.Osteoporoza je najčešća metabolička bolest kostiju, obilježena smanjenom koštanom masom i poremećenom koštanom mikroarhitekturom. Prikladan životinjski model za istraživanje osteoporoze su ovarijektomirani miševi. Kako bismo pobliže istražili mehanizme smanjene koštane formacije i pojačane koštane razgradnje nakon ovarijektomije, proveli smo pokuse ekspresijskog profiliranja koristeći se uzorcima kostiju ovarijektomiranih miševa soja C57BL/6J. Nakon ovarijektomije pojačava se izražaj gena uključenih u imunološki odgovor, regulaciju staničnog ciklusa, apoptozu i koštanu razgradnju, dok se ekspresija gena bitnih za mitozu, metabolizam ugljikohidrata, razvoj kosti, strukturu izvanstaničnog matriksa i angiogenezu smanjuje. Od koštano specifičnih gena, interleukin 7 (IL-7), receptor za IL-7 i matriks metalopeptidazu 8 imali su pojačan izražaj, dok je za transformirajući čimbenik rasta -beta 3, prokolagen tipa I i tipa VI uočen smanjen genski izražaj. Također smo otkrili smanjen izražaj dvaju gena, i to receptora 1 za paratireoidni hormon i WD ponavljajuću domenu 5, koji su bitni za koštani razvoj, a promjena njihove regulacije nije do sada primijećena u osteoporozi. Kako bismo dodatno istražili obogaćenost pojedinih funkcionalnih skupina gena u kostima ovarijetkomiranih životinja, podatke smo analizirali s pomoću algoritma gene set enrichment analysis (GSEA). Zaključno, ovarijektomija značajno utječe na izražaj brojnih gena uključenih u različite biološke procese, što potvrđuje pretpostavku da mnogi molekularni putovi imaju važnu ulogu u patofiziologiji osteoporoze

EEG ANALYSIS AND SPECT IMAGING IN ALZHEIMER’S DISEASE, VASCULAR DEMENTIA AND MILD COGNITIVE IMPAIRMENT

Background: Alzheimer’s disease (AD) and vascular dementia (VaD) represent a leading public-health problem given the rising age of the population. Early diagnosis of dementia, especially at the stage of mild cognitive impairment (MCI) has become an important goal of the modern patient work-up. Brain perfusion single-photon emission computed tomography (SPECT) has become a mainstay of diagnostic algorithms in patients with dementia showing specific patterns of hypoperfusion in temporal and parietal lobes. Clinical electroencephalography (EEG) is a relatively simple and inexpensive diagnostic tool showing potential in assessing cortical thinning and lower perfusion in temporoparoetal regions. Subjects and methods: Our study was a cross sectional and included retrospective analysis of the group of patients diagnosed with AD, VaD and MCI. The study group consisted of 50 patients - 29 females and 21 males. All patients underwent EEG and SPECT analysis as part of regular work-up. Result: Patients with AD exhibit EEG changes mostly in the form of theta waves, focal abnormalities and spike-and-wave complexes in frontotemporal regions with the reduction in the amplitude of alpha waves. SPECT in most patients exhibited hypoperfusion in temporoparietal regions with occasional unilateral abnormalities in frontotemporal region. EEG changes in patients with VaD are predominantly in the form of theta waves while SPECT findings show mostly “patchy” abnormalities. EEG readings are normal or exhibit minimal changes in the group of patients with MCI, while SPECT imaging exhibits mostly normal CBF. Conclusion: EEG and SPECT are diagnostic methods which show specific changes, especially in AD. EEG can be used to monitor the therapeutic effect and progression of AD as well as the possible transition from MCI to early stage AD. SPECT on the other hand, being a more expensive and less available method, can be utilized as an add-on method to increase the specificity and sensitivity of the diagnostic algorithm

Predictive value of cerebrospinal fluid visinin-like protein-1 levels for Alzheimer's disease early detection and differential diagnosis in patients with mild cognitive impairment

Visinin-like protein 1 (VILIP-1) recently emerged as a potential biomarker of Alzheimer's disease (AD). This neuronal calcium sensor protein previously used as a marker of acute ischemic stroke is elevated in the cerebrospinal fluid (CSF) of AD patients. The goal of this study was to assess CSF VILIP-1 potential in early AD diagnosis and in differentiating mild cognitive impairment (MCI) patients with and without risk of AD. Additionally, we tested VILIP-1 ability to differentiate AD from other primary causes of dementia, and predict the progression of AD-related cognitive decline. VILIP-1 levels were compared with five CSF AD biomarkers (t-tau, Aβ1-42, p-tau181, p-tau199, and p-tau231). VILIP-1 successfully differentiated two MCI patient groups characterized by absence or presence of pathological levels of these CSF biomarkers, except for t-tau. VILIP-1/Aβ(1-42) and VILIP-1/p-tau181 ratios also differentiated MCI patients with pathological CSF biomarker levels. However, there was no difference in VILIP-1 levels between AD and MCI patients. VILIP-1/Aβ(1-42) and VILIP-1/p-tau231 ratios reached high sensitivities (above 70%) and very high specificities (above 85%) in differentiating AD patients from HC. Additionally, VILIP-1 differentiated AD from patients with Lewy body disease with 77.1% sensitivity and 100% specificity. VILIP-1 potential as a prognostic biomarker of cognitive decline in AD was also proved since VILIP-1/t-tau, VILIP-1/p-tau181, and VILIP-1/p-tau231 ratios correlated with MMSE scores. These data indicate that VILIP-1 alone or in combination with other AD CSF biomarkers represent a valuable marker for the early diagnosis of AD, recognition of MCI patients at higher risk to develop dementia, and in differentiating AD from LBD

The Centenary Progress of Molecular Genetics. A 100th Anniversary of T. H. Morgan’s Discoveries

A century ago, Thomas Hunt Morgan, the American scientist, studied the cytogenetic changes of drosophila and came to cytogenetic explanation of Mendel’s basic laws of genetic heredity. These studies resulted in today’s Mendel-Morgan chromosomal theory of heredity. On the occasion of the hundredth anniversary of this important discovery the authors have decided to give a review of the most significant achievments in the field of molecular genetics until the completion of the Human Genome Project. The most important points concerning the technology of DNA recombination and genetic engineering are also presented. The final section discusses the significance of previous achievements of molecular genetics in biomedicine and other related fields. There is also a tabular presentation of the sequence of the most important findings in the field of molecular genetics through time