Abstract
Original language | English |
---|---|
Pages (from-to) | 2182-2196 |
Number of pages | 15 |
Journal | Alzheimer's & Dementia |
Volume | 19 |
Issue number | 5 |
Early online date | 1 Jan 2023 |
DOIs | |
Publication status | Published - May 2023 |
Keywords
- COERULEUS MRI CONTRAST
- NUCLEUS RAPHE DORSALIS
- BRAIN-STEM NUCLEI
- LOCUS-COERULEUS
- NORADRENERGIC MODULATION
- A-BETA
- NEUROFIBRILLARY TANGLES
- CHOLINERGIC INNERVATION
- COGNITIVE DECLINE
- AMINERGIC NUCLEI
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- 10.1002/alz.12937Licence: CC BY
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In: Alzheimer's & Dementia, Vol. 19, No. 5, 05.2023, p. 2182-2196.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART
AU - Ehrenberg, A.J.
AU - Kelberman, M.A.
AU - Liu, K.Y.
AU - Dahl, M.J.
AU - Weinshenker, D.
AU - Falgas, N.
AU - Dutt, S.
AU - Mather, M.
AU - Ludwig, M.
AU - Betts, M.J.
AU - Winer, J.R.
AU - Teipel, S.
AU - Weigand, A.J.
AU - Eschenko, O.
AU - Hammerer, D.
AU - Leiman, M.
AU - Counts, S.E.
AU - Shine, J.M.
AU - Robertson, I.H.
AU - Levey, A.I.
AU - Lancini, E.
AU - Son, G.
AU - Schneider, C.
AU - Van Egroo, M.
AU - Liguori, C.
AU - Wang, Q.
AU - Vazey, E.M.
AU - Rodriguez-Porcel, F.
AU - Haag, L.
AU - Bondi, M.W.
AU - Vanneste, S.
AU - Freeze, W.M.
AU - Yi, Y.J.
AU - Maldinov, M.
AU - Gatchel, J.
AU - Satpati, A.
AU - Babiloni, C.
AU - Kremen, W.S.
AU - Howard, R.
AU - Jacobs, H.I.L.
AU - Grinberg, L.T.
N1 - Funding Information: This manuscript was facilitated by the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART), through the Neuromodulatory Subcortical System professional interest area (PIA). The views and opinions expressed by authors in this publication represent those of the authors and do not necessarily reflect those of the PIA membership, ISTAART, or the Alzheimer's Association. The authors wish to acknowledge the following funding sources: (A.J.E.) NIH T32GM139780, UC Berkeley Greater Good Science Center; (M.A.K.) NIA F31AG069502; (D.W.) NIA R01AG062581, NIA RF1AG061175; (N.F.) Alzheimer's Association AACSF-21-723056, Global Brain Health Institute, Alzheimer's Association and Alzheimer's Society UK GBHI-ALZ-UK-21-723831; (K.Y.L.) Medical Research Council UK MR/S021418/1; (M.M.) NIH R01AG025340; (M.J.B.) Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Project-ID 425899996 – SFB 1436 Project A08 and the German Federal Ministry of Education and Research (BMBF, funding code 01ED2102B) under the aegis of JPND; (S.D.) NSF GRFP DGE1418060; (D.H.) CRC 1436, CRC 1315, ARUK SRF 2018B-004, CBBS Neural Network 17; (J.R.W.) NIA F32AG074625, NIA P30AG066515; (M.Le.) Deutsche Forschungsgemeinschaft Project-ID 42589994; (S.E.C.) NIH P01G014449-24, NIH P30AG072931-06, NIH R01AG060731-04; (J.M.S.) NHMRC 1193857, The University of Sydney, Viertel/Bellberry Foundation; (A.I.L.) P30AG066511, U54AG065187, U01AG061357; (E.L.) Deutsche Forschungsgemeinschaft 362321501, Deutsche Forschungsgemeinschaft RTG2413; (M.Lu.) European Regional Development Fund ZS/2016/04/78113; (M.V.E.) BrightFocus Foundation A20211016F; (Q.W.) NIH RF1AG067729, NIH R01AG064664, NIH RF1 AG056815; (E.M.V.) U01AA025481-05S1; (J.R.G.) NIA K23AG058805; (W.F.) Alzheimer Nederland WE.03-2018-13; (C.B.) European Committee HORIZON-INFRA-2021-TECH-01-01 GAP-101058516, European Committee H2021-MSCA-DN-2021; (D.H.) CRC 1436, CRC 1315, ARUK SRF 2018B-004, CBBS Neural Network 17; (W.S.K.) NIA R01AG050595, NIA R01AG076838; (H.I.L.J.) NIH R01AG062559, NIH R01AG068062, NIH R21AG074220, Alzheimer's Association AARG-22-920434, Alzheimer Nederland WE.03-2019-02; (L.T.G.) NIH K24AG053435, R01AG060477, R01 AG064314, R01AG070826, R01AG056573. Funding Information: This manuscript was facilitated by the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART), through the Neuromodulatory Subcortical System professional interest area (PIA). The views and opinions expressed by authors in this publication represent those of the authors and do not necessarily reflect those of the PIA membership, ISTAART, or the Alzheimer's Association. The authors wish to acknowledge the following funding sources: (A.J.E.) NIH T32GM139780, UC Berkeley Greater Good Science Center; (M.A.K.) NIA F31AG069502; (D.W.) NIA R01AG062581, NIA RF1AG061175; (N.F.) Alzheimer's Association AACSF‐21‐723056, Global Brain Health Institute, Alzheimer's Association and Alzheimer's Society UK GBHI‐ALZ‐UK‐21‐723831; (K.Y.L.) Medical Research Council UK MR/S021418/1; (M.M.) NIH R01AG025340; (M.J.B.) Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Project‐ID 425899996 – SFB 1436 Project A08 and the German Federal Ministry of Education and Research (BMBF, funding code 01ED2102B) under the aegis of JPND; (S.D.) NSF GRFP DGE1418060; (D.H.) CRC 1436, CRC 1315, ARUK SRF 2018B‐004, CBBS Neural Network 17; (J.R.W.) NIA F32AG074625, NIA P30AG066515; (M.Le.) Deutsche Forschungsgemeinschaft Project‐ID 42589994; (S.E.C.) NIH P01G014449‐24, NIH P30AG072931‐06, NIH R01AG060731‐04; (J.M.S.) NHMRC 1193857, The University of Sydney, Viertel/Bellberry Foundation; (A.I.L.) P30AG066511, U54AG065187, U01AG061357; (E.L.) Deutsche Forschungsgemeinschaft 362321501, Deutsche Forschungsgemeinschaft RTG2413; (M.Lu.) European Regional Development Fund ZS/2016/04/78113; (M.V.E.) BrightFocus Foundation A20211016F; (Q.W.) NIH RF1AG067729, NIH R01AG064664, NIH RF1 AG056815; (E.M.V.) U01AA025481‐05S1; (J.R.G.) NIA K23AG058805; (W.F.) Alzheimer Nederland WE.03‐2018‐13; (C.B.) European Committee HORIZON‐INFRA‐2021‐TECH‐01‐01 GAP‐101058516, European Committee H2021‐MSCA‐DN‐2021; (D.H.) CRC 1436, CRC 1315, ARUK SRF 2018B‐004, CBBS Neural Network 17; (W.S.K.) NIA R01AG050595, NIA R01AG076838; (H.I.L.J.) NIH R01AG062559, NIH R01AG068062, NIH R21AG074220, Alzheimer's Association AARG‐22‐920434, Alzheimer Nederland WE.03‐2019‐02; (L.T.G.) NIH K24AG053435, R01AG060477, R01 AG064314, R01AG070826, R01AG056573. Publisher Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2023/5
Y1 - 2023/5
N2 - 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. HighlightsNeuromodulatory 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.
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. HighlightsNeuromodulatory 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 - COERULEUS MRI CONTRAST
KW - NUCLEUS RAPHE DORSALIS
KW - BRAIN-STEM NUCLEI
KW - LOCUS-COERULEUS
KW - NORADRENERGIC MODULATION
KW - A-BETA
KW - NEUROFIBRILLARY TANGLES
KW - CHOLINERGIC INNERVATION
KW - COGNITIVE DECLINE
KW - AMINERGIC NUCLEI
U2 - 10.1002/alz.12937
DO - 10.1002/alz.12937
M3 - Article
C2 - 36642985
SN - 1552-5260
VL - 19
SP - 2182
EP - 2196
JO - Alzheimer's & Dementia
JF - Alzheimer's & Dementia
IS - 5
ER -