Selection of controls in the study of human neurodegenerative diseases in old age

Human post-mortem brain tissue, mostly provided by brain banks, is precious because most human neurodegenerative diseases are restricted in their complete forms to human beings. However, the agonal state, post-mortem delay between death and tissue processing, variable vulnerability of chromatin, RNAs, proteins and metabolites can compromise the usability of the tissue material. Such factors must be considered and assessed in every experimental approach. The use of controls for comparative purposes to analyze diseased cases is crucial as the basic conditions of controls must be the same as those encountered in problem cases. Age, gender, region, hemisphere, and clear characterisation of objective neuropathological changes (e.g., Alzheimer's disease stages of Braak and Braak) in matching controls and problem cases must be considered in every study, and data must be clearly specified when presenting materials and methods in publications. Additional care must be taken regarding atypical neurodegenerative alterations, concomitant pathologies, and systemic diseases, together with drug consumption and treatments. The absence of neurological and mental symptoms and signs, although a sine qua non condition, is not sufficient to match control and problem cases for research.