P4‐320: Amyloid‐beta Accumulation Affects in Vivo Staging of Tau Deposition in Cognitively Impaired Individuals
Year: 2019
Type: article
Abstract: Several recent tau PET based studies have explored the interaction between amyloid-beta (Aβ) deposition and the spread of tau pathology. Pontecorvo et al., (2017) showed higher tau-PET tracer uptake in Aβ positive mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects relative to respective Aβ negative subjects. Schwarz et al., (2016) showed Aβ positive subjects in both the MCI and AD groups had higher estimated Braak stages. We further investigate this interaction using an approach that estimates the most likely sequence of tau spread without relying on regional abnormality cut-points. We show the benefit of fine-grained staging in identifying subjects in the earliest stages of amyloid dependent tau pathology. We used cross-sectional tau PET data from 344 subjects (201 cognitively normal / 109 MCI / 34 AD) within the Alzheimer's Disease Neuroimaging Initiative (ADNI), using the earliest available data-point for each subject. We downloaded the UC Berkeley flortaucipir (AV-1451) dataset (version 2018-10-15) from the ADNI website (https://ida.loni.usc.edu), containing partial volume corrected regional SUVRs (Baker et al., 2017; Maass et al., 2017). The dataset also contains SUVR information for composite regions as defined in (aggregated) Braak stages (I/II, III/IV and V/VI). We normalized all SUVRs by the inferior cerebellar grey matter reference region and corrected each for sex, education level and race (white/not Hispanic versus other). We used the latest (up to two years prior) demographic, diagnostic and amyloid burden (florbetapir, AV-45) information from the ADNIMERGE dataset, also available on the ADNI website. We used the event based model (EBM; Young et al., 2014) to find the most likely ordering of tau abnormality in the progression from normal cognition to diagnosed AD. Our models identified the expected spread of tau pathology (Figure 1). Aβ positivity increased the fraction of MCI subjects at higher stages (Figures 2 and 3). The fine-grained model identified more CN and MCI subjects with early tau pathology, particularly among Aβ positive subjects (Figure 4).
Source: Alzheimer s & Dementia
Institution: University College London
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980757487