Basic pathologies of neurodegenerative dementias and their relevance for state-of-the-art molecular imaging studies.

INTRODUCTION: Rising life-expectancy in the modern society has resulted in a rapidly growing prevalence of dementia, particularly of Alzheimer's disease (AD). Dementia turns into one of the most common age-related disorders with deleterious consequences for the concerned patients and their relatives, as well as worrying effects on the socio-economic systems. These facts justify strengthened scientific efforts to identify the pathologic origin of dementing disorders, to improve diagnosis, and to interfere therapeutically with the disease progression. BASIC PATHOLOGIES: In the recent years, remarkable progress has been made concerning the identification of molecular mechanisms underlying the pathology of neurodegenerative disorders. Growing evidence indicates that a common basis of many neurodegenerative dementias can be found in increased production, misfolding and pathological aggregation of proteins, such as beta-amyloid, tau protein, a-synuclein, or the recently described ubiquitinated TDP-43. This progressive insight in pathological processes is paralleled by the development of new therapeutic approaches. However, the exact contribution or mechanism of different pathologies with regard to the development of disease is not yet sufficiently clear. Considerable overlap of pathologies has been documented in different types of clinically defined dementias post mortem, and it has been difficult to correlate post mortem histopathology data with disease-expression during life. Molecular imaging procedures may play a valuable role to circumvent this limitation. RELEVANCE FOR IMAGING STUDIES: In general, methods of molecular imaging have recently experienced an impressive advance, with numerous new and improved technologies emerging. These exciting tools may play a key role in the future regarding the evaluation of pathomechanisms, preclinical evaluation of new diagnostic procedures in animal models, selection of patients for clinical trials, and therapy monitoring. In this overview, molecular key pathologies, which are currently regarded to be strongly associated with the development of different dementias, will be shortly summarized; it will also be discussed how state-of-the-art imaging technology can assist to visualize these processes now and in the future.