2023
DOI: 10.1186/s13195-023-01178-w
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Initial levels of β-amyloid and tau deposition have distinct effects on longitudinal tau accumulation in Alzheimer’s disease

Abstract: Background To better assist with the design of future clinical trials for Alzheimer’s disease (AD) and aid in our understanding of the disease’s symptomatology, it is essential to clarify what roles β-amyloid (Aβ) plaques and tau tangles play in longitudinal tau accumulation inside and outside the medial temporal lobe (MTL) as well as how age, sex, apolipoprotein E (APOE) ε4 (APOE-ε4), and Klotho-VS heterozygosity (KL-VShet) modulate these relationships. Methods … Show more

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Cited by 13 publications
(9 citation statements)
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“…These therapies are more likely to be effective when introduced before substantial tau aggregation. 2,11,54,55 Our results showed that our plasma mid-p-tau181 could discriminate between tau-positive and -negative subjects with a specificity greater than 85%, and that plasma mid-p-tau levels showed a significant linear correlation with tau PET tracer retention in patients with AD continuum. Therefore, reasonable estimation of brain tau accumulation by using plasma levels of mid-p-tau181 could identify patients with high plasma mid-ptau levels, in whom brain tau aggregation has been suggested to have progressed beyond the critical point, and could thereby help select patients with low-to-moderate tau burden who are more likely to benefit from DMTs targeting Aβ, like so in the phase 3 study of donanemab.…”
Section: Discussionmentioning
confidence: 55%
See 1 more Smart Citation
“…These therapies are more likely to be effective when introduced before substantial tau aggregation. 2,11,54,55 Our results showed that our plasma mid-p-tau181 could discriminate between tau-positive and -negative subjects with a specificity greater than 85%, and that plasma mid-p-tau levels showed a significant linear correlation with tau PET tracer retention in patients with AD continuum. Therefore, reasonable estimation of brain tau accumulation by using plasma levels of mid-p-tau181 could identify patients with high plasma mid-ptau levels, in whom brain tau aggregation has been suggested to have progressed beyond the critical point, and could thereby help select patients with low-to-moderate tau burden who are more likely to benefit from DMTs targeting Aβ, like so in the phase 3 study of donanemab.…”
Section: Discussionmentioning
confidence: 55%
“…These therapies are more likely to be effective when introduced before substantial tau aggregation. 2,11,54,55 Therefore, identifying patients with high plasma mid-p-tau levels, in whom brain tau aggregation has been suggested to have progressed beyond the critical point, could help select patients more likely to benefit from DMTs targeting Aβ, like so in the phase 3 study of donanemab. 11 Our results showed that our plasma mid-p-tau181 could discriminate between tau-positive and -negative subjects with a specificity greater than 85%, effectively excluding patients with advanced tau pathology.…”
Section: Discussionmentioning
confidence: 99%
“…Conversely, in the tau deposition-speci c brain regions (e.g., hippocampus, amygdala, and inferior temporal gyrus), this correlation was in uenced more by the T state. This might possibly be attributed to the in uence of Aβ and tau protein deposition on neurodegeneration in these brain regions 33 . At earlier stages of the disease (A-T-), there might be parts of the brain that have not yet developed signi cant Aβ deposits and tau neuro brillary tangles.…”
Section: Discussionmentioning
confidence: 99%
“…It's important to highlight that particular regions of interest (ROIs) that show early tau deposition can be valuable in aiding the early detection of Alzheimer's disease (AD) 50 . Moreover, as per the National Institute on Aging (NIH) report, Alzheimer's disease initially damages neurons and their connections in brain regions associated with memory, later extending its impact to the cerebral cortex areas responsible for language, cognition, and social behavior 51 .…”
Section: Discussionmentioning
confidence: 99%