1. Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART
- Author
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Alexander J. Ehrenberg, Michael A. Kelberman, Kathy Y. Liu, Martin J. Dahl, David Weinshenker, Neus Falgàs, Shubir Dutt, Mara Mather, Mareike Ludwig, Matthew J. Betts, Joseph R. Winer, Stefan Teipel, Alexandra J. Weigand, Oxana Eschenko, Dorothea Hämmerer, Marina Leiman, Scott E. Counts, James M. Shine, Ian H. Robertson, Allan I. Levey, Elisa Lancini, Gowoon Son, Christoph Schneider, Maxime Van Egroo, Claudio Liguori, Qin Wang, Elena M. Vazey, Federico Rodriguez‐Porcel, Lena Haag, Mark W. Bondi, Sven Vanneste, Whitney M. Freeze, Yeo‐Jin Yi, Mihovil Maldinov, Jennifer Gatchel, Abhijit Satpati, Claudio Babiloni, William S. Kremen, Robert Howard, Heidi I. L. Jacobs, Lea T. Grinberg, Psychology 2, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Psychiatrie & Neuropsychologie
- Subjects
COERULEUS MRI CONTRAST ,BRAIN-STEM NUCLEI ,Epidemiology ,Health Policy ,CHOLINERGIC INNERVATION ,NUCLEUS RAPHE DORSALIS ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,AMINERGIC NUCLEI ,Developmental Neuroscience ,NORADRENERGIC MODULATION ,LOCUS-COERULEUS ,COGNITIVE DECLINE ,Neurology (clinical) ,ddc:610 ,Geriatrics and Gerontology ,NEUROFIBRILLARY TANGLES ,A-BETA - Abstract
The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.
- Published
- 2023
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