Associations between plasma p‐tau217, in vivo brain pathology and cognition in individuals with autosomal‐dominant Alzheimer's disease: Findings from the Colombia‐Boston (COLBOS) biomarker study. (31st December 2021)

• Record Type: Journal Article
• Authors: Aguillon, David; Vila‐Castelar, Clara; Chen, Yinghua; Su, Yi; Chen, Kewei; Hansson, Oskar; Dage, Jeffrey L.; Janelidze, Shorena; Zetterberg, Henrik; Baena, Ana Y.; Gómez‐Henck, Clara; Fox‐Fuller, Joshua T.; Sanchez, Justin S.; Sperling, Reisa A.; Johnson, Keith A.; Blennow, Kaj; Reiman, Eric M.; Lopera, Francisco; Quiroz, Yakeel T.
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.056260
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Diagnostic methods available for in‐vivo diagnosis of Alzheimer's disease (AD) are expensive and invasive. Interest in plasma P‐tau217 has recently grown as it seems to have higher diagnostic accuracy for clinical AD, compared to other blood biomarkers in preclinical stages. We recently showed that carriers of autosomal dominant AD due to the PSEN1‐E280A mutation had increased plasma P‐tau217 levels, approximately 20 years prior their estimated onset of mild cognitive impairment. Here, we examined whether baseline levels of plasma P‐tau217 may predict subsequent levels of in vivo cortical amyloid‐β, regional tau pathology, and memory performance in PSEN1 ‐E280A carriers and non‐carriers. Methods: A total of 24 PSEN1 ‐E280A carriers (mean age = 31.13 ± 6.81 years), including 18 cognitively‐unimpaired and 6 with MCI, and 20 age‐matched non‐carriers (mean age = 27.55 ± 6.99) from the Colombia‐Boston (COLBOS) biomarker study were included. Participants underwent blood sampling at baseline and PiB‐PET, Flortaucipir‐PET, and memory testing after 8.95±4.19 years of follow‐up. Plasma P‐tau217 concentrations were measured using a highly sensitive immunoassay. Linear regressions were used to examine associations of baseline P‐tau217 levels with subsequent in vivo amyloid, tau levels in the brain and memory scores each, with age, sex, carrier group membership and time from baseline to follow‐up examinations as covariates. Results: Compared to non‐carriers, mutation carriers had higher P‐tau217 levels (carriers: 5.27±4.69, non‐carriers: 2.53±1.39; p=0.016), greater regional tau (e.g. entorhinal cortex, inferior temporal tau; p <0.0001) and cortical amyloid (p <0.0001), and lower memory scores (e.g. CERAD Word List Recall; p=0.001). Higher baseline P‐tau217 levels were associated with subsequent elevations in in vivo amyloid and tau pathology and memory decline in carriers (Figure 1). Conclusion: Findings suggest that baseline levels of plasma P‐tau217 may predict subsequent levels of in vivo amyloid and tau burden, as well as memory decline in PSEN1‐E280A carriers and non‐carriers. These findings provide further support for plasma P‐tau217 as a potential non‐invasive diagnostic and prognostic biomarker of AD, which could be useful in clinical practice and trials.