Creutzfeldt-Jakob, Parkinson, Lewy Body Dementia and Alzheimer Diseases: From Diagnosis to Therapy

Abstract

Depositions of proteins in form of amyloid and non-amyloid plaques are common pathogenic signs of more than 20 degenerative diseases affecting the central nervous system or a variety of peripheral tissues. Among the neuropathological conditions, Alzheimer's, Parkinson's and the prion diseases, such as Creutzfeldt-Jakob disease (CJD), present ambiguities as regarding their differential diagnosis. At present, their diagnosis must be confirmed by post-mortem examination of the brain. Currently the ante-mortem diagnosis is still based on the integration of multiple data (clinical, paraclinical and biological analyses) because no unique marker exists for such diseases. The detection of specific biomarkers would be useful to develop a differential diagnostic, distinguishing not only different neurodegenerative diseases but also the disease from the non-pathological effects of aging. Several neurodegenerative biomarkers are present at very low levels during the early stages of the disease development and their ultra-low detection is needed for early diagnosis, which should permit more effective therapeutic interventions, before the disease concerned can progress to a stage where considerable damage to the brain has already occurred. In the case of prion diseases, there are concerns regarding not only patient care, but the wider community too, with regard to the risk of transmission of prions, especially during blood transfusion, for which, four cases of variant CJD infection associated with transfusion of non-leukocyte-depleted blood components have been confirmed. Therefore the development of techniques with high sensitivity and specificity represent the major challenge in the field of the protein misfolding diseases. In this paper we review the current analytical and/or biochemical diagnostic technologies used mainly in prion, but also in Alzheimer and Parkinson diseases and emphasizing work on the protein detection as a surrogates and specific biomarker in the body fluid of patients (urine, CSF and blood). This review highlights the urgency of the development of early and sensitive diagnostics in terms of therapeutic challenge.

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

“…During the past years, great efforts have been made to identify reliable biomarkers for AD in body fluids of patients that are suitable for minimal invasive early diagnosis of AD, mainly cerebrospinal fluid (CSF) and blood. Recently, we've summarized all of the criteria needed to establish convenient technique with the following advantages (Dupiereux et al (2009): a. Low-cost b. Rapid-fast c. Good level of accuracy 6.…”

Reduced cGMP levels in CSF of AD patients correlate with severity of dementia and current depression

“…Thus, selective inhibition of PDEs could offer novel approaches in the therapy of people suffering from dementia. To monitor therapy and to determine disease development and progression, one focus in biomedical research of neurodegenerative diseases is the identification of novel biomarkers [12, 13]. Further, because the CSF compartment is close to the neuropathological changes due to AD, this makes it the preferred body fluid for identifying novel biomarkers for brain-related diseases.…”

CSF Concentrations of cAMP and cGMP Are Lower in Patients with Creutzfeldt-Jakob Disease but Not Parkinson's Disease and Amyotrophic Lateral Sclerosis

“…To date, clinical or even preclinical biomarkers for neurodegenerative diseases such as PD, ALS, CJD are desirable and in the focus of biomedical research [9], [10]. A biomarker as defined by the National Institutes of Health is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” [11].…”