Tharick A Pascoal1, Sulantha Mathotaarachchi1, Monica Shin1, Andrea L Benedet2, Sara Mohades1, Seqian Wang1, Tom Beaudry1, Min Su Kang1, Jean-Paul Soucy3, Aurelie Labbe4, Serge Gauthier5, Pedro Rosa-Neto6. 1. Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada. 2. Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada; CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil. 3. Montreal Neurological Institute, Montreal, Canada. 4. Douglas Hospital Research Centre, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada. 5. AD Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, Canada; McGill University, Montreal, Canada. 6. Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada; Montreal Neurological Institute, Montreal, Canada; AD Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, Canada; McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. Electronic address: pedro.rosa@mcgill.ca.
Abstract
INTRODUCTION: Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia. METHODS: We stratified 314 mild cognitive impairment individuals using [18F]florbetapir positron emission tomography Aβ imaging and cerebrospinal fluid p-tau. Regression and voxel-based logistic regression models with interaction terms evaluated 2-year changes in cognition and clinical status as a function of baseline biomarkers. RESULTS: We found that the synergism between [18F]florbetapir and p-tau, rather than their additive effects, was associated with the cognitive decline and progression to AD. Furthermore, voxel-based analysis revealed that temporal and inferior parietal were the regions where the synergism determined an increased likelihood of developing AD. DISCUSSION: Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between Aβ and p-tau proteins.
INTRODUCTION: Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia. METHODS: We stratified 314 mild cognitive impairment individuals using [18F]florbetapir positron emission tomography Aβ imaging and cerebrospinal fluid p-tau. Regression and voxel-based logistic regression models with interaction terms evaluated 2-year changes in cognition and clinical status as a function of baseline biomarkers. RESULTS: We found that the synergism between [18F]florbetapir and p-tau, rather than their additive effects, was associated with the cognitive decline and progression to AD. Furthermore, voxel-based analysis revealed that temporal and inferior parietal were the regions where the synergism determined an increased likelihood of developing AD. DISCUSSION: Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between Aβ and p-tau proteins.
Authors: Dunja Mrdjen; Edward J Fox; Syed A Bukhari; Kathleen S Montine; Sean C Bendall; Thomas J Montine Journal: Acta Neuropathol Date: 2019-08-07 Impact factor: 17.088
Authors: Tharick A Pascoal; Andrea L Benedet; Dana L Tudorascu; Joseph Therriault; Sulantha Mathotaarachchi; Melissa Savard; Firoza Z Lussier; Cécile Tissot; Mira Chamoun; Min Su Kang; Jenna Stevenson; Gassan Massarweh; Marie-Christine Guiot; Jean-Paul Soucy; Serge Gauthier; Pedro Rosa-Neto Journal: Brain Date: 2021-12-16 Impact factor: 15.255