Network interdigitations of Tau and amyloid-beta deposits define cognitive levels in aging
Kim, Chan-Mi (Massachusetts General Hospital (Boston))
Montal, Victor (Institut d'Investigació Biomèdica Sant Pau)
Diez, Ibai (Massachusetts General Hospital (Boston))
Orwig, William (Massachusetts General Hospital (Boston))
Sepulcre, Jorge (Massachusetts General Hospital (Boston))
Universitat Autònoma de Barcelona

Data:	2021
Resum:	Amyloid-beta (Aβ) plaques and tau neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD); their contribution to neurodegeneration and clinical manifestations are critical in understanding preclinical AD. At present, the mechanisms related to Aβ and tau pathogenesis leading to cognitive decline in older adults remain largely unknown. Here, we examined graph theory-based positron emission tomography (PET) analytical approaches, within and between tau and Aβ PET modalities, and tested the effects on cognitive changes in cognitively normal older adults (CN). Particularly, we focused on the network interdigitations of Aβ and tau deposits, along with cognitive test scores in CN at both baseline and 2-year follow-up (FU). We found highly significant Aβ-tau network integrations in AD vulnerable areas, as well as significant associations between those Aβ-tau interdigitations and general cognitive impairment in CN at baseline and FU. Our findings suggest a distinctive contribution of interlinking network relationships between Aβ and tau deposits in heteromodal areas of the human brain. They support a network-based interaction between Aβ and tau accumulations as a key factor for cognitive deterioration in CN prior to dementia. We examined network interaction patterns within single positron emission tomography (PET) modality, such as Aß-to-Aß or Tau-to-Tau correlations, and between different PET modalities, such as Aß-to-Tau or Tau-to-Aß, at high-resolution (voxel-level) in cognitively normal older adults (CN), using a graph theory-based analysis. We observed that the PET uptakes derived from Aß-to-Tau interdigitations were significantly associated with Alzheimer's Disease Assessment Scale-Cognitive Subscale in AD vulnerable brain areas, a finding confirmed by our longitudinal investigation. Therefore, our work suggests the preceding contribution of network interactions between Aß and tau deposits to explain initial cognitive changes in CN prior to the conversion of dementia.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Aging ; Alzheimer's disease ; Amyloid PET ; Cognition ; Connectivity analysis ; Tau PET
Publicat a:	Human brain mapping, Vol. 42 (may 2021) , p. 2990-3004, ISSN 1097-0193

DOI: 10.1002/hbm.25350
PMID: 33955621

15 p, 6.3 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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