Publications (3)7.47 Total impact
Article: Biochemical studies in Normal Pressure Hydrocephalus (NPH) patients: change in CSF levels of amyloid precursor protein (APP), amyloid-beta (Aβ) peptide and phospho-tau.[show abstract] [hide abstract]
ABSTRACT: Normal Pressure Hydrocephalus (NPH) is one of the causes of dementia of the elderly characterized by impaired mental function, gait difficulties and urinary incontinence. Previously, it was proposed that some of the NPH patients may develop Alzheimer's disease (AD) like pathology. Aim of this study was to compare levels of different CSF biomarkers, including total secreted β-amyloid precursor protein (sAPP), sAPP-alpha form (sAPPα), amyloid-beta (Aβ) peptide, total-tau protein and hyperphosphorylated-tau protein in subjects from NPH and Non-NPH Control (NNC). CSF was collected from 23 NPH patients and 13 Non-NPH controls by lumber puncture. Western blot analysis was performed to measure levels of sAPP-total. ELISA was used separately to determine levels of sAPPα, Aβ peptide, total-tau and phospho-tau proteins. We found a significant decrease in levels of total secreted APP, sAPPα and Aβ (1-42) in the CSF sample of NPH patients vs. NNC. We did not observe any change in levels of total-tau or phospho-tau in NPH vs. NNC subjects. Notably, phospho-tau level was significantly increased in the NPH patients, who were suffering from the disease for more than one year, vs. NNC. Among five biomarkers studied, decreased sAPP, sAPPα and Aβ (1-42) levels in CSF can be molecular markers to distinguish NPH cases from NNC. Disease severity can also be assessed by increased levels of CSF phospho-tau protein and the ratio of phospho-tau to Aβ (1-42), which might be a useful tool for predicting conversion of NPH individuals to other neurodegenerative disorders including Alzheimer's disease (AD).Journal of psychiatric research 04/2011; 45(4):539-47. · 3.72 Impact Factor
Article: Neuropathological and immunochemical studies of brain parenchyma in acetylcholinesterase knockout mice: implications in Alzheimer's disease.[show abstract] [hide abstract]
ABSTRACT: The 'cholinergic hypothesis', based on the correlation of the reduction of cholinergic activity in Alzheimer's disease (AD) with cognition and memory, is currently the most widely-held view for AD. Drug treatments for AD focus mainly on inhibition of acetylcholinesterase (AChE), and to some extent butyrylcholinesterase (BChE). In addition to changes in AChE in AD, there is a rise in the level of the sister enzyme BChE. However, the role of the two cholinesterases is poorly understood in vivo. We characterized several proteins immunohistochemically in brain sections from AChE nullizygote (AChE-/-) and wild type AChE+/+ mice. Previous studies had shown that AChE-/- mouse tissues are devoid of AChE activity and that the overall cholinesterase activity is significantly decreased in the knockout group . Despite the differences of cholinesterase activity, we found no significant structural alterations between the experimental groups. Immunohistochemical examination revealed no neuronal, dendritic, astrocytic, synaptic, microglial, and endothelial differences between AChE-/- and AChE+/+ mice. Similarly, the histochemical examination showed no morphologic alterations between AChE-/- and AChE+/+ mice. Our studies show that neither the absence of AChE nor the presence exclusively of BChE is associated with neuroglial and vascular pathology.Journal of Alzheimer's disease: JAD 08/2007; 11(4):481-9. · 3.74 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Muscle biopsy is an important and essential tool in the diagnosis and treatment of muscle disease. For several de-cades, histological staining of paraffin-embedded tissue was used in muscle pathology. In the past few decades, fresh-frozen enzyme histochemical techniques have become the standard for assessing muscle disease. They have been complemented by the use of electron microscopy to char-acterize ultrastructural changes. More recently, the discov-ery of certain muscle proteins and the development of an-tibodies made possible the combination of enzyme histochemical and immunohistochemical methods to better assess muscle changes. In this review, we discuss the roles of histochemistry, enzyme histochemistry, immunohisto-chemistry, and electron microscopy in the diagnosis of skel-etal muscle pathology (The J Histotechnol 31:101, 2008). Introduction A muscle biopsy involves obtaining a tissue sample that will be processed and examined under a light microscope for pathological alterations in muscle, connective tissue, and blood vessels. Although muscle biopsies have been per-formed since the 19th century, they did not become a stan-dard diagnostic tool until the mid-20th century (1). Earlier biopsy procedures illustrate the difficulties in ob-taining appropriate skeletal muscle specimens for morpho-logic examination. Because contraction artifacts can distort the morphology of muscle fibers, particularly skeletal muscle, sutures were inserted into each end of the muscle in situ and attached to a wooden applicator to "splint" the tissue sample obtained for microscopic evaluation (2). This pro-cedure has been replaced by more-sophisticated and less-invasive methods. At present, muscle biopsies (3–8) normally are performed with the patient under local anesthetic. He or she may ex-perience a burning sensation from the anesthetic, "tugging" during the procedure, and soreness in the area for a week after the procedure (9). Current methods of muscle biopsy include needle biopsy, in which a hollow needle is inserted through the skin and the appropriate tissue is aspirated (10–14). In many cases, open muscle biopsy is used to obtain fresh and frozen tissue specimens to be used in his-tochemical, immunohistochemical, and electron microscopy protocols (15).