TY - JOUR
T1 - Local molecular and connectomic contributions of tau-related neurodegeneration
AU - for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
AU - Nabizadeh, Fardin
AU - Furst, Ansgar J.
AU - Taylor, Joy L.
AU - Yesavage, Jerome A.
AU - Li, Gail
AU - Petrie, Eric C.
AU - Peskind, Elaine R.
AU - Harding, Sandra
AU - Fruehling, JJay
AU - Massoglia, Dino
AU - James, Olga
AU - Arfanakis, Konstantinos
AU - Fleischman, Debra
AU - Friedl, Karl
AU - Finley, Shannon
AU - Hayes, Jacqueline
AU - Morrison, Rosemary
AU - Davis, Melissa
AU - Grafman, Jordan
AU - Neylan, Thomas
AU - Raj, Balebail Ashok
AU - Fargher, Kristin
AU - Smith, Amanda
AU - Raudin, Lisa
AU - Chaing, Gloria
AU - Relkin, Norman
AU - Smith, Karen Elizabeth
AU - Shim, Hyungsub
AU - Ponto, Laura L.Boles
AU - Schultz, Susan K.
AU - Sarrael, Antero
AU - Hernando, Raymundo
AU - Pomara, Nunzio
AU - Drost, Dick
AU - Rachinsky, Irina
AU - Pasternak, Stephen
AU - Bachman, David
AU - Spicer, Kenneth
AU - Mintzer, Jacobo
AU - Miller, Bruce L.
AU - Rosen, Howard J.
AU - Correia, Stephen
AU - Malloy, Paul
AU - Salloway, Stephen
AU - Tremont, Geoffrey
AU - Querfurth, Henry
AU - Ott, Brian R.
AU - Watkins, Franklin
AU - Garg, Pradeep
AU - Williamson, Jeff D.
AU - Sink, Kaycee M.
AU - Schwartz, Eben S.
AU - Kitzmiller, Tamar J.
AU - Santulli, Robert B.
AU - Anderson, Karen
AU - Blank, Karen
AU - Pearlson, Godfrey D.
AU - Brown, Alice D.
AU - Celmins, Dzintra
AU - Zimmerman, Earl A.
AU - Adeli, Anahita
AU - Kataki, Maria
AU - Scharre, Douglas W.
AU - Rainka, Michelle
AU - Capote, Horacio
AU - Bates, Vernice
AU - Reeder, Stephanie
AU - Tariot, Pierre
AU - Nguyen, Dana
AU - Preda, Adrian
AU - Carlsson, Cynthia M.
AU - Asthana, Sanjay
AU - Johnson, Sterling
AU - Bartha, Rob
AU - Lee, T. Y.
AU - Borrie, Michael
AU - Kittur, Smita
AU - DeCarli, Charles
AU - Olichney, John
AU - Carmichae, Owen
AU - Fletcher, Evan
AU - Hudson, Leon
AU - Ogrocki, Paula
AU - Lerner, Alan
AU - Allard, Joanne
AU - Johnson, Patricia Lynn
AU - Norbash, Alexander
AU - Budson, Andrew E.
AU - Killiany, Ronald
AU - Kowall, Neil
AU - Sirrel, Sherye A.
AU - Jacobson, Sandra A.
AU - Belden, Christine M.
AU - Sabbagh, Marwan N.
AU - Tinklenberg, Jared
AU - Rosen, Allyson
AU - Lane, Barton
AU - Frey, Meghan
AU - Marshall, Gad
AU - Johnson, Keith A.
AU - Sperling, Reisa A.
AU - Reynolds, Brigid
AU - Johnson, Kathleen
AU - Turner, Raymond Scott
AU - Villena, Teresa
AU - Martinez, Walter
AU - Sadowsky, Carl
AU - Johnson, Nancy
AU - Wu, Chuang Kuo
AU - Lipowski, Kristine
AU - Kerwin, Diana
AU - Trost, Dick
AU - Rogers, John
AU - Kertesz, Andrew
AU - Munic, Donna
AU - Bernick, Charles
AU - Assaly, Michele
AU - Mudge, Benita
AU - Feldman, Howard
AU - Hsiung, Ging Yuek Robin
AU - Hosein, Chris
AU - Bergman, Howard
AU - Chertkow, Howard
AU - MacAvoy, Martha G.
AU - Carson, Richard E.
AU - van Dyck, Christopher H.
AU - Hunt, Cynthia
AU - Herring, Scott
AU - Matthews, Brandy R.
AU - Hake, Ann Marie
AU - Farlow, Martin R.
AU - Johnson, Heather
AU - Kendall, Tracy
AU - Parfitt, Francine
AU - Graff-Radford, Neill R.
AU - Bartzokis, George
AU - Lu, Po H.
AU - Silverman, Daniel H.S.
AU - Woo, Ellen
AU - Tingus, Kathleen
AU - Apostolova, Liana
AU - Swerdlow, Russell H.
AU - Anderson, Heather S.
AU - Burns, Jeffrey M.
AU - Cellar, Janet S.
AU - Lah, James J.
AU - Levey, Allan I.
AU - DeVous, Michael
AU - Martin-Cook, Kristen
AU - Weiner, Myron
AU - King, Richard
AU - Diaz-Arrastia, Ramon
AU - Quiceno, Mary
AU - Mathews, Dana
AU - Womack, Kyle
AU - McAdams-Ortiz, Catherine
AU - Thai, Gaby
AU - Mulnard, Ruth A.
AU - Brand, Connie
AU - Ismail, MSaleem
AU - Makino, Kelly M.
AU - Martin, Kim
AU - Goldstein, Bonnie S.
AU - Porsteinsson, Anton P.
AU - Simpson, Donna M.
AU - Oakley, Mary Ann
AU - Lopez, Oscar L.
AU - Conrad, Gary
AU - Oates, Elizabeth
AU - Sinha, Partha
AU - Hardy, Peter
AU - Jicha, Greg
AU - Smith, Charles D.
AU - Wolk, David
AU - Karlawish, Jason H.
AU - Arnold, Steven E.
AU - Wong, Terence Z.
AU - Petrella, Jeffrey R.
AU - Doraiswamy, PMurali
AU - De Santi, Susan
AU - Glodzik, Lidia
AU - de Leon, Mony J.
AU - Rusinek, Henry
AU - Michel, Christina A.
AU - Cerbone, Brittany
AU - Galvin, James E.
AU - Kielb, Stephanie
AU - D’Agostino, Daniel
AU - Onyike, Chiadi
AU - Roberts, Peggy
AU - Greig, Maria T.
AU - Varon, Daniel
AU - Duara, Ranjan
AU - Shah, Raj C.
AU - de Toledo-Morrell, Leyla
AU - Mitsis, Effie
AU - Grossman, Hillel
AU - Ances, Beau
AU - Holtzman, David
AU - Raichle, Marcus
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to American Aging Association 2024.
PY - 2024
Y1 - 2024
N2 - Neurodegeneration in Alzheimer’s disease (AD) is known to be mostly driven by tau neurofibrillary tangles. However, both tau and neurodegeneration exhibit variability in their distribution across the brain and among individuals, and the relationship between tau and neurodegeneration might be influenced by several factors. I aimed to map local molecular and connectivity characteristics that affect the association between tau pathology and neurodegeneration. The current study was conducted on the cross-sectional tau-PET and longitudinal T1-weighted MRI scan data of 186 participants from the ADNI dataset including 71 cognitively unimpaired (CU) and 115 mild cognitive impairment (MCI) individuals. Furthermore, the normative molecular profile of a region was defined using neurotransmitter receptor densities, gene expression, T1w/T2w ratio (myelination), FDG-PET (glycolytic index, glucose metabolism, and oxygen metabolism), and synaptic density. I found that the excitatory-inhibitory (E:I) ratio, myelination, synaptic density, glycolytic index, and functional connectivity are linked with deviation in the relationship between tau and neurodegeneration. Furthermore, there was spatial similarity between tau pathology and glycolytic index, synaptic density, and functional connectivity across brain regions. The current study demonstrates that the regional susceptibility to tau-related neurodegeneration is associated with specific molecular and connectomic characteristics of the affected neural systems. I found that the molecular and connectivity architecture of the human brain is linked to the different effects of tau pathology on downstream neurodegeneration.
AB - Neurodegeneration in Alzheimer’s disease (AD) is known to be mostly driven by tau neurofibrillary tangles. However, both tau and neurodegeneration exhibit variability in their distribution across the brain and among individuals, and the relationship between tau and neurodegeneration might be influenced by several factors. I aimed to map local molecular and connectivity characteristics that affect the association between tau pathology and neurodegeneration. The current study was conducted on the cross-sectional tau-PET and longitudinal T1-weighted MRI scan data of 186 participants from the ADNI dataset including 71 cognitively unimpaired (CU) and 115 mild cognitive impairment (MCI) individuals. Furthermore, the normative molecular profile of a region was defined using neurotransmitter receptor densities, gene expression, T1w/T2w ratio (myelination), FDG-PET (glycolytic index, glucose metabolism, and oxygen metabolism), and synaptic density. I found that the excitatory-inhibitory (E:I) ratio, myelination, synaptic density, glycolytic index, and functional connectivity are linked with deviation in the relationship between tau and neurodegeneration. Furthermore, there was spatial similarity between tau pathology and glycolytic index, synaptic density, and functional connectivity across brain regions. The current study demonstrates that the regional susceptibility to tau-related neurodegeneration is associated with specific molecular and connectomic characteristics of the affected neural systems. I found that the molecular and connectivity architecture of the human brain is linked to the different effects of tau pathology on downstream neurodegeneration.
KW - Alzheimer’s disease
KW - Connectivity
KW - Mild cognitive impairment
KW - Molecular
KW - Neurodegeneration
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=85205268273&partnerID=8YFLogxK
U2 - 10.1007/s11357-024-01339-1
DO - 10.1007/s11357-024-01339-1
M3 - Article
C2 - 39343862
AN - SCOPUS:85205268273
SN - 2509-2715
JO - GeroScience
JF - GeroScience
ER -