Distinct tau PET patterns in atrophy‐defined subtypes of Alzheimer's disease

Abstract

Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) "typical", (2) "limbic-predominant", (3) "hippocampal-sparing", and (4) "mild atrophy". We examined the neurobiological characteristics and clinical progression of these atrophydefined subtypes. Methods:The four subtypes were replicated using a clustering method on MRI data in 260 amyloid--positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [ 18 F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typicalThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. c ○ 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. Alzheimer's Dement. 2020;16:335-344. wileyonlinelibrary.com/journal/alz 335 336 OSSENKOPPELE ET AL.

Predicting future rates of tau accumulation on PET

“…2 and Supplementary Table 2 ) is consistent with the longitudinal tau PET study of Pontecorvo et al (2019) . It is also conceptually consistent with clinical observations that younger onset Alzheimer’s disease has a faster, more aggressive clinical course ( Koss et al , 1996 ; Cho et al , 2017 ; Ossenkoppele et al , 2019 a ; La Joie et al , 2020 ). The rate of tau accumulation among the oldest impaired individuals (i.e.…”

“…2 and Supplementary Table 2 ). This set of variables is characteristic of early onset Alzheimer’s disease ( Koss et al , 1996 ; Ho et al , 2002 ; Cho et al , 2017 ; Scholl et al , 2017 ; Ossenkoppele et al , 2019 a ). While our main focus was on tau rates, Fig.…”

“…1 also demonstrates that the highest baseline tau levels were found in younger impaired individuals. Very high cross-sectional tau PET SUVR values are characteristic of early onset Alzheimer’s disease ( Cho et al , 2017 ; Scholl et al , 2017 ; Ossenkoppele et al , 2019 a ). This set of predictors of high tau accumulation rates coupled with generally lower burden of non-Alzheimer’s disease pathologies at younger age ( Nelson et al , 2011 ) leads to the conclusion that early onset Alzheimer’s disease might be a highly advantageous group in which to conduct clinical trials that examine the feasibility of targeting tau-related mechanisms.…”

Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer’s disease

“…This discrepancy may be attributable to the disproportionate frequency of the ε4 allele in different subtypes of AD. The hippocampal sparing type of AD is associated with a younger age at onset, lower frequency of the ApoE ε4 allele, greater tau burden particularly in the parietal cortex, faster cortical atrophy, and faster cognitive decline than the typical AD subtype [36][37][38][39]. Therefore, we suspect that the inclusion of a greater proportion of the hippocampal sparing subtype in the study cohort diluted an effect of ε4 on tau burden or even caused contrary results.…”

Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer’s disease

“…This discrepancy may be attributable to the disproportionate frequency of the ε4 allele in patients with different subtypes of AD. The hippocampal sparing type of AD is associated with a younger age at onset, a lower frequency of the ApoE ε4 allele, greater tau burden particularly in the parietal cortex, faster cortical atrophy, and faster cognitive decline than the typical AD subtype [36][37][38][39]. Therefore, we suspect that inclusion of a greater proportion of the hippocampal sparing subtype in the study cohort diluted the effect of ε4 on the tau burden, or may even have caused contrary results.…”