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The accumulation rate of tau aggregates is higher in females and younger individuals
Author(s) -
Smith Ruben,
Strandberg Olof,
Mattsson Niklas,
Leuzy Antoine,
Palmqvist Sebastian,
Pontecorvo Michael J.,
Devous Michael D.,
Ossenkoppele Rik,
Hansson Oskar
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043876
Subject(s) - dementia , cohort , medicine , psychology , tau pathology , cognitive impairment , nuclear medicine , alzheimer's disease , pathology , disease
Background Tau pathology is a key hallmark of Alzheimer’s disease (AD), but factors modifying the rate of tau accumulation are still largely unknown. Tau‐PET allows tau pathology to be visualized in vivo in AD. Our aim was to study factors associated with the accumulation rate of tau pathology, using [ 18 F]flortaucipir PET. Method 419 participants from four longitudinal cohorts in the United States (AVID05, n=157; Expedition 3, n=82; and ADNI, n=123) and Sweden (n=57) were scanned between June 2014 and May 2019. Study participants were cognitively unimpaired (CU, n=153), or patients with mild cognitive impairment (MCI, n=139) or AD with dementia (AD, n=127).Participants underwent two to four [ 18 F]‐flortaucipir PET scans with a mean of 538 (±163[SD]) days between the first and last scan. Amyloid‐β(Aβ) status was determined using PET. [ 18 F]‐flortaucipir was quantified in a temporal meta‐region of interest (ROI) and a neocortical ROI. Subject‐specific slopes (reflecting annual change) of [ 18 F]‐flortaucipir SUVR were derived from linear regression models for each ROI. Generalized linear models were used to predict the subject‐specific slopes using the following variables: diagnostic group, age, sex, baseline tau‐PET SUVR, baseline Aβ‐status, APOE‐ε4 status and study cohort. Result Accelerated increase in [ 18 F]‐flortaucipir retention was observed in Aβ+ MCI and AD dementia, respectively, when compared to either Aβ‐ CU and Aβ‐ MCI (Figure 1). We found associations between change in [ 18 F]‐flortaucipir over time and female sex (temporal meta‐ROI: t=2.93, p=0.004; neocortical ROI: t=2.96, p=0.003), younger age (temporal‐meta ROI: t=‐2.42, p=0.02), and baseline [ 18 F]‐flortaucipir retention (temporal‐meta ROI: t=3.60, p<0.001; neocortical ROI: t=4.88, p<0.001) (Figure 2). There was a significant interaction between age and Aβ‐status on change in [ 18 F]‐flortaucipir SUVR (temporal‐meta ROI: t=‐2.50, p=0.013). There was no effect of study cohort or APOE‐ε4 genotype. In a similar analysis on longitudinal Aβ‐PET (in ADNI subjects only, n=639) we found significant associations between the rate of Aβ‐accumulation and APOE‐ε4 positivity, older age and baseline Aβ‐positivity, but no effect of sex. Conclusion These findings indicate that the tau accumulation rate is increased in females and Aβ‐positive younger individuals, in contrast to Aβ‐accumulation which is increased in APOE‐ε4 carriers and older individuals.