Lowe, Val J.

ObjectiveTo investigate β‐amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients.MethodsPatients with MS (n = 16) and controls (n = 80) matched for age, sex, andAPOEε4 status from the population‐based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVrs) from the entire cortex and previously determined Alzheimer disease (AD) signature regions in the same population were calculated for group comparisons and testing for associations with age.ResultsAD signature PiB SUVr (odds ratio [OR] [95% confidence interval (CI)] = 0.52 [0.27–0.98],p= 0.044), total cortical PiB SUVr (OR [95% CI] = 0.52 [0.28–0.99],p= 0.048), and the frequency of abnormal PiB SUVrs (OR [95% CI] = 0.10 [0.01–0.90],p= 0.040) were lower in MS than controls. Although AD‐signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (OR [95% CI] = 10.65 [1.10–103.35],p= 0.041) in MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.14 [−0.023 to −0.006],p= 0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (estimate [95% CI] = −0.13 [−0.021 to −0.005],p= 0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls.InterpretationAlthough both β‐amyloid and tau are biomarkers of cognitive aging and AD, cortical β‐amyloid deposition was lower in MS than age‐matched controls, suggesting that some aspect of MS pathobiology retards the accumulation of β‐amyloid but not the accumulation of tau.ANN NEUROL 2020;87:556–567

AbstractIntroductionWe previously characterized associations between brain imaging measurements of amyloid‐β (Aβ) plaque burden and apolipoprotein E (APOE) ε4 gene dose in a small number of cognitively unimpaired late‐middle‐aged APOE ε4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross‐sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements, classifications, and associations with age in a larger number of unimpaired HMs, HTs, and NCs over a wider age range.MethodsWe analyzed 11C Pittsburgh compound B (Aβ) positron emission tomography (PET), flortaucipir (tau) PET, and volumetric magnetic resonance imaging data from 164 study participants of age 47–86 years, including 26 APOE ε4 HMs, 48 HTs, and 90 NCs matched for age and sex.ResultsAβ PET measurements rose, plateaued at the respective ages of 68 and 76, and then declined with age in unimpaired HM and HT groups. Compared with NCs, these two groups began to have significantly higher Aβ PET measurements at ages 62 and 70, respectively, and no longer had significantly higher measurements by ages 71 and 78, respectively. They began to have significantly higher entorhinal cortex tau PET measurements at ages 66 and 70, respectively, and no longer had significantly higher measurements by ages 74 and 78, respectively. Brain atrophy measurements tended to decline slowly with age in all three genetic groups. Their elevated tau PET measurements were attributable to those with positive Aβ PET scans. 41.0%, 18.0%, and 5.0% of the 47‐ to 70‐year‐old HMs, HTs, and NCs and 25.0%, 79.0%, and 38.0% of the 71‐ to 86‐year‐old HMs, HTs, and NCs had positive Aβ PET scans, and the long‐term recall memory scores are significantly higher in the older HMs than in HT and NC groups, suggesting resistance to Aβ deposition in those HMs who remained unimpaired at older ages.ConclusionsThis study provides information about Aβ plaque burden, tau tangle burden, and neurodegeneration in cognitively unimpaired persons at three levels of genetic risk for AD. Unimpaired APOE ε4 HMs can be studied before their 70s to evaluate the understanding of factors, processes, and interventions involved in the predisposition to and prevention of AD, and after their 70s, to discover factors, processes, and interventions involved in the resilience or resistance to and prevention of AD.

AbstractIntroductionComparison of tau (flortaucipir) positron emission tomography (FTP‐PET) to autopsy is important to demonstrate the relationship of FTP‐PET to neuropathologic findings.MethodsAutopsies were performed on 26 participants who had antemortem FTP‐PET. FTP‐PET standardized uptake value ratios (SUVRs) were compared to autopsy diagnoses and Braak tangle stage. Quantitative tau burden was compared to regional FTP‐PET signal.ResultsParticipants with Braak stages of IV or greater had elevated FTP‐PET signal. FTP‐PET was elevated in participants with Alzheimer's disease. An FTP‐PET SUVR cut point of 1.29 was determined to be optimal. Quantitative measurements of hippocampal and temporal lobe tau burden were highly correlated to FTP‐PET signal (rho's from 0.61 to 0.70, P ≤ .02).DiscussionElevated FTP‐PET reflects Braak IV or greater neuropathology. Participants with primary age‐related tauopathy and hippocampal sclerosis did not show elevated FTP‐PET signal. Secondary neuropathologic diagnoses of Alzheimer's disease neuropathologic change can lead to borderline elevated FTP‐PET signal.