ISTAART Community

This PIA brings together expertise from diverse disciplines with the focus on understanding the biology and function of the subcortical nuclei and their role in the pathogenesis of AD and other tauopathies.  Subcortical nuclei in brainstem, basal forebrain, thalamus and hypothalamus, including the locus coeruleus, dorsal raphe nucleus, and cholinergic basal forebrain nucleus are the first critical sites in the brain to accumulate AD-tau pathology. Further work in humans and animal models showed that early AD-tau driven degeneration of these areas has clinical impact preceding cognitive decline and may exacerbate AD progression in the brain. In addition, degeneration of subcortical nuclei is closely linked to the build-up of cerebral amyloid in AD, but also to different upstream pathological lesions in other neurodegenerative diseases. Thus, functional and structural disintegration of subcortical nuclei and related neuronal networks may critically drive the downstream expression, including remote cortical degeneration and clinical phenotype, from different pathologies. Yet, despite their importance in early stages of AD and other neurodegenerative diseases, these structures that are also critically involved in arousal, sleep, memory, attention, and various neuropsychiatric symptoms are still underexplored.