In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S5 ( 2020-12)
Abstract:
Several studies contend that some Alzheimer’s disease (AD) subjects develop early‐stage tau pathology before amyloid pathology 1,2 , supporting a hypothesis that there are multiple distinct subtypes of amyloid and tau pathology progression within AD. We investigated this hypothesis, applying data‐driven disease subtyping models to both amyloid and tau PET as well as CSF measures. Method We performed two separate analyses using cross‐sectional data from ADNI. The first was a tau‐PET‐based analysis, which used eight regional amyloid PET (AV‐45) SUVRs and ten tau PET (AV‐1451) SUVRs from 402 subjects with both scans at the same visit. The second was a tau‐CSF‐based analysis, substituting CSF‐based prediction of tau PET SUVR (see Figure 2) in place of actual tau PET to give a larger dataset of 996 subjects. We used the Subtype and Stage Inference (SuStaIn 3 ) algorithm to infer disease progression subtypes and individuals’ disease stages, and characterized demographic, cognitive and CSF differences across subtypes. Result We found two PET‐based subtypes in the tau‐PET‐based analysis: an amyloid‐first (84% of subjects) subtype and a tau‐first (16% of subjects) subtype in which Braak stage I‐III related tau SUVRs (hippocampus, amygdala, entorhinal cortex) become abnormal first (Figure 1A,B). The tau‐CSF‐based analysis confirms these subtypes: amyloid‐first (83% of subjects) and tau‐first (17% of subjects; Figure 2A,B). There were no significant differences in demographics or subject stages between subtypes in the tau‐PET‐based analysis (Figure 1C,D). In the tau‐CSF‐based analysis there was a small difference in age (amyloid‐first subjects 2.4 years older, Cohen’s f 2 = 0.02, p 〈 0.05). Amyloid‐first individuals also had slightly worse executive function (Cohen’s f 2 = 0.02, p 〈 0.05; Figure 3C) and, as expected, more abnormal CSF amyloid (Cohen’s f 2 = 0.10, p 〈 0.001; Figure 3D) while tau‐first individuals had more abnormal CSF tau (Cohen’s f 2 = 0.06, p 〈 0.001; Figure 3D). Conclusion We identified amyloid‐first and tau‐first AD subtypes consistently across PET and CSF biomarkers. Our data‐driven approach supports the existence of a subtype of AD with tau accumulation prior to amyloid pathology. References: 1. Duyckaerts, et al., 2015, Acta Neuropath; 2. Weigand, et al., 2019, Brain Comm; 3. Young, et al., 2018, Nature Comm.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
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