TY  - JOUR
AU  - Ehrenberg, Alexander J
AU  - Kelberman, Michael A
AU  - Liu, Kathy Y
AU  - Dahl, Martin J
AU  - Weinshenker, David
AU  - Falgàs, Neus
AU  - Dutt, Shubir
AU  - Mather, Mara
AU  - Ludwig, Mareike
AU  - Betts, Matthew J
AU  - Winer, Joseph R
AU  - Teipel, Stefan
AU  - Weigand, Alexandra J
AU  - Eschenko, Oxana
AU  - Hämmerer, Dorothea
AU  - Leiman Algranati, Marina
AU  - Counts, Scott E
AU  - Shine, James M
AU  - Robertson, Ian H
AU  - Levey, Allan I
AU  - Lancini, Elisa
AU  - Son, Gowoon
AU  - Schneider, Chrisoph
AU  - Egroo, Maxime Van
AU  - Liguori, Claudio
AU  - Wang, Qin
AU  - Vazey, Elena M
AU  - Rodriguez-Porcel, Federico
AU  - Haag, Lena
AU  - Bondi, Mark W
AU  - Vanneste, Sven
AU  - Freeze, Whitney M
AU  - Yi, Yeo-Jin
AU  - Maldinov, Mihovil
AU  - Gatchel, Jennifer
AU  - Satpati, Abhijit
AU  - Babiloni, Claudio
AU  - Kremen, William S
AU  - Howard, Robert
AU  - Jacobs, Heidi I L
AU  - Grinberg, Lea T
TI  - Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.
JO  - Alzheimer's and dementia
VL  - 19
IS  - 5
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2023-00160
SP  - 2182-2196
PY  - 2023
AB  - 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.
KW  - Humans
KW  - Alzheimer Disease: pathology
KW  - Brain: pathology
KW  - Biomarkers
KW  - Disease Progression
KW  - Biomarkers (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10182252
C6  - pmid:36642985
DO  - DOI:10.1002/alz.12937
UR  - https://pub.dzne.de/record/194973
ER  -