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@ARTICLE{Ehrenberg:194973,
author = {Ehrenberg, Alexander J and Kelberman, Michael A and Liu,
Kathy Y and Dahl, Martin J and Weinshenker, David and
Falgàs, Neus and Dutt, Shubir and Mather, Mara and Ludwig,
Mareike and Betts, Matthew J and Winer, Joseph R and Teipel,
Stefan and Weigand, Alexandra J and Eschenko, Oxana and
Hämmerer, Dorothea and Leiman Algranati, Marina and Counts,
Scott E and Shine, James M and Robertson, Ian H and Levey,
Allan I and Lancini, Elisa and Son, Gowoon and Schneider,
Chrisoph and Egroo, Maxime Van and Liguori, Claudio and
Wang, Qin and Vazey, Elena M and Rodriguez-Porcel, Federico
and Haag, Lena and Bondi, Mark W and Vanneste, Sven and
Freeze, Whitney M and Yi, Yeo-Jin and Maldinov, Mihovil and
Gatchel, Jennifer and Satpati, Abhijit and Babiloni, Claudio
and Kremen, William S and Howard, Robert and Jacobs, Heidi I
L and Grinberg, Lea T},
title = {{P}riorities for research on neuromodulatory subcortical
systems in {A}lzheimer's disease: {P}osition paper from the
{NSS} {PIA} of {ISTAART}.},
journal = {Alzheimer's and dementia},
volume = {19},
number = {5},
issn = {1552-5260},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DZNE-2023-00160},
pages = {2182-2196},
year = {2023},
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.},
keywords = {Humans / Alzheimer Disease: pathology / Brain: pathology /
Biomarkers / Disease Progression / Biomarkers (NLM
Chemicals)},
cin = {AG Düzel / AG Teipel},
ddc = {610},
cid = {I:(DE-2719)5000006 / I:(DE-2719)1510100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10182252},
pubmed = {pmid:36642985},
doi = {10.1002/alz.12937},
url = {https://pub.dzne.de/record/194973},
}