Abnormal tau in amyloid PET negative individuals.
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ABSTRACT:
SUBMITTER: Yoon B
PROVIDER: S-EPMC9695003 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Abnormal tau in amyloid PET negative individuals.
Yoon Bora B Guo Tengfei T Provost Karine K Korman Deniz D Ward Tyler J TJ Landau Susan M SM Jagust William J WJ
Neurobiology of aging 20210930
We examined the characteristics of individuals with biomarker evidence of tauopathy but without β-amyloid (Aβ) (A-T+) in relation to individuals with (A+T+) and without (A-T-) evidence of Alzheimer's disease (AD). We included 561 participants with Aβ and tau PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We compared A-T- (n = 316), A-T+ (n = 63), and A+T+ (n = 182) individuals on demographics, amyloid, tau, hippocampal volumes, and cognition. A-T+ individuals were low on apolip ...[more]
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Project description:A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A+) and tau PET-positive (T+) in the medial temporal lobe (A+TMTL+) and/or in the temporal neocortex (A+TNEO-T+) and compared them with A+T- and A-T- groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the A+TNEO-T+ (hazard ratio (HR) = 19.2, 95% confidence interval (CI) = 10.9-33.7), A+TMTL+ (HR = 14.6, 95% CI = 8.1-26.4) and A+T- (HR = 2.4, 95% CI = 1.4-4.3) groups versus the A-T- (reference) group. Both A+TMTL+ (HR = 6.0, 95% CI = 3.4-10.6) and A+TNEO-T+ (HR = 7.9, 95% CI = 4.7-13.5) groups also showed faster clinical progression to mild cognitive impairment than the A+T- group. Linear mixed-effect models indicated that the A+TNEO-T+ (β = -0.056 ± 0.005, T = -11.55, P < 0.001), A+TMTL+ (β = -0.024 ± 0.005, T = -4.72, P < 0.001) and A+T- (β = -0.008 ± 0.002, T = -3.46, P < 0.001) groups showed significantly faster longitudinal global cognitive decline compared to the A-T- (reference) group (all P < 0.001). Both A+TNEO-T+ (P < 0.001) and A+TMTL+ (P = 0.002) groups also progressed faster than the A+T- group. In summary, evidence of advanced Alzheimer's disease pathological changes provided by a combination of abnormal amyloid and tau PET examinations is strongly associated with short-term (that is, 3-5 years) cognitive decline in cognitively unimpaired individuals and is therefore of high clinical relevance.
| S-EPMC9671808 | biostudies-literature
Project description:In Alzheimer's disease, the molecular pathogenesis of the extracellular Aβ-amyloid (Aβ) instigation of intracellular tau accumulation is poorly understood. We employed a high-resolution PET scanner, with low detection thresholds, to examine the Aβ-tau association using a convolutional neural network (CNN), and compared results to a standard voxel-wise linear analysis. The full range of Aβ Centiloid values was highly predicted by the tau topography using the CNN (training R2 = 0.86, validation R2 = 0.75, testing R2 = 0.72). Linear models based on tau-SUVR identified widespread positive correlations between tau accumulation and Aβ burden throughout the brain. In contrast, CNN analysis identified focal clusters in the bilateral medial temporal lobes, frontal lobes, precuneus, postcentral gyrus and middle cingulate. At low Aβ levels, information from the middle cingulate, frontal lobe and precuneus regions was more predictive of Aβ burden, while at high Aβ levels, the medial temporal regions were more predictive of Aβ burden. The data-driven CNN approach revealed new associations between tau topography and Aβ burden.
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Project description:PurposeAssess the individual and combined diagnostic value of amyloid-PET and tau-PET in a memory clinic population.MethodsClinical reports of 136 patients were randomly assigned to two diagnostic pathways: AMY-TAU, amyloid-PET is presented before tau-PET; and TAU-AMY, tau-PET is presented before amyloid-PET. Two neurologists independently assessed all reports with a balanced randomized design, and expressed etiological diagnosis and diagnostic confidence (50-100%) three times: (i) at baseline based on the routine diagnostic workup, (ii) after the first exam (amyloid-PET for the AMY-TAU pathway, and tau-PET for the TAU-AMY pathway), and (iii) after the remaining exam. The main outcomes were changes in diagnosis (from AD to non-AD or vice versa) and in diagnostic confidence.ResultsAmyloid-PET and tau-PET, when presented as the first exam, resulted in a change of etiological diagnosis in 28% (p = 0.006) and 28% (p < 0.001) of cases, and diagnostic confidence increased by 18% (p < 0.001) and 19% (p < 0.001) respectively, with no differences between exams (p > 0.05). We observed a stronger impact of a negative amyloid-PET versus a negative tau-PET (p = 0.014). When added as the second exam, amyloid-PET and tau-PET resulted in a further change in etiological diagnosis in 6% (p = 0.077) and 9% (p = 0.149) of cases, and diagnostic confidence increased by 4% (p < 0.001) and 5% (p < 0.001) respectively, with no differences between exams (p > 0.05).ConclusionAmyloid-PET and tau-PET significantly impacted diagnosis and diagnostic confidence in a similar way, although a negative amyloid-PET has a stronger impact on diagnosis than a negative tau-PET. Adding either of the two as second exam further improved diagnostic confidence.Trial numberPB 2016-01346.
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