TY - JOUR
T1 - Blood Phosphorylated Tau 181 as a Biomarker for Amyloid Burden on Brain PET in Cognitively Healthy Adults
AU - McGrath, Emer R.
AU - Beiser, Alexa S.
AU - O'Donnell, Adrienne
AU - Yang, Qiong
AU - Ghosh, Saptaparni
AU - Gonzales, Mitzi M.
AU - Himali, Jayandra J.
AU - Satizabal, Claudia L.
AU - Johnson, Keith A.
AU - Tracy, Russell P.
AU - Seshadri, Sudha
N1 - Funding Information:
This research was supported by the Health Research Board of Ireland (CSF-2020-011) and the Alzheimer’s Association (AACSF-18-566570). The Framingham Heart Study is supported by the NHL BI (contract no. N01-HC-25195, no. HHSN2682 01500001, and no. 75N92019D00031). This research was also supported by NHLBI grants R01 HL60040 and R01 HL70100, grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033193, U01 AG049505, U01 AG052409) and grants from the National Institute of Neurological Disorders and Stroke (NS017950 and UH2 NS100605).
Funding Information:
This research was supported by the Health Research Board of Ireland (CSF-2020-011) and the Alzheimer's Association (AACSF-18-566570). The Framingham Heart Study is supported by the NHLBI (contract no. N01-HC-25195, no. HHSN268201500001, and no. 75N92019D00031). This research was also supported by NHLBI grants R01 HL60040 and R01 HL70100, grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033193, U01 AG049505, U01 AG052409) and grants from the National Institute of Neurological Disorders and Stroke (NS017950 and UH2 NS100605).
Publisher Copyright:
© 2022 - IOS Press. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Background: Plasma phosphorylated-tau181 (p-tau181) is a promising biomarker for Alzheimer's disease (AD) and may offer utility for predicting preclinical disease. Objective: To evaluate the prospective association between plasma p-tau181 and amyloid-β (Aβ) and tau-PET deposition in cognitively unimpaired individuals. Methods: Plasma p-tau181 levels were measured at baseline in 52 [48% women, mean 64.4 (SD 5.5) years] cognitively unimpaired Framingham Offspring cohort participants using samples stored between 2011-2014 who subsequently underwent 11C-Pittsburgh Compound-B (PiB)-PET and/or 18F-Flortaucipir (FTP)-PET scans (n = 18 with tau-PET) a mean of 6.8 (SD 0.6) years later. Our primary outcomes included Aβ-precuneus, Aβ-FLR (frontal, lateral, and retrosplenial cortices) and tau-global composite region PET deposition. Secondary outcomes included individual regional Aβ and tau PET-deposition. P-tau181 was compared with plasma neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in predicting PET outcomes. Results: P-tau181 was associated with increased Aβ deposition in the FLR (β±SE, 1.25±0.30, p < 0.0001), precuneus (1.35±0.29, p < 0.001), and other cortical regions. Plasma NFL (1.30±0.49, p = 0.01) and GFAP (1.46±0.39, p < 0.001) were also associated with FLR Aβ deposition. In models including all three biomarkers adjusted for age, sex, APOE E4 allele, AD polygenic risk score and cortical atrophy score, p-tau181 (0.93±0.31, p < 0.01, R2 = 0.18) and GFAP (0.93±0.41, p = 0.03, R2 = 0.11), but not NFL (0.25±0.51, p = 0.62, R2 = 0.01), were associated with FLR-Aβ deposition. Plasma p-tau181 was not associated with tau-PET burden. Conclusion: In cognitively unimpaired adults, elevated plasma p-tau181 is associated with future increased Aβ deposition across multiple brain regions. Our results highlight the potential utility of p-tau181 as a blood-biomarker to screen for brain-amyloid deposition in cognitively healthy individuals in a community-setting.
AB - Background: Plasma phosphorylated-tau181 (p-tau181) is a promising biomarker for Alzheimer's disease (AD) and may offer utility for predicting preclinical disease. Objective: To evaluate the prospective association between plasma p-tau181 and amyloid-β (Aβ) and tau-PET deposition in cognitively unimpaired individuals. Methods: Plasma p-tau181 levels were measured at baseline in 52 [48% women, mean 64.4 (SD 5.5) years] cognitively unimpaired Framingham Offspring cohort participants using samples stored between 2011-2014 who subsequently underwent 11C-Pittsburgh Compound-B (PiB)-PET and/or 18F-Flortaucipir (FTP)-PET scans (n = 18 with tau-PET) a mean of 6.8 (SD 0.6) years later. Our primary outcomes included Aβ-precuneus, Aβ-FLR (frontal, lateral, and retrosplenial cortices) and tau-global composite region PET deposition. Secondary outcomes included individual regional Aβ and tau PET-deposition. P-tau181 was compared with plasma neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in predicting PET outcomes. Results: P-tau181 was associated with increased Aβ deposition in the FLR (β±SE, 1.25±0.30, p < 0.0001), precuneus (1.35±0.29, p < 0.001), and other cortical regions. Plasma NFL (1.30±0.49, p = 0.01) and GFAP (1.46±0.39, p < 0.001) were also associated with FLR Aβ deposition. In models including all three biomarkers adjusted for age, sex, APOE E4 allele, AD polygenic risk score and cortical atrophy score, p-tau181 (0.93±0.31, p < 0.01, R2 = 0.18) and GFAP (0.93±0.41, p = 0.03, R2 = 0.11), but not NFL (0.25±0.51, p = 0.62, R2 = 0.01), were associated with FLR-Aβ deposition. Plasma p-tau181 was not associated with tau-PET burden. Conclusion: In cognitively unimpaired adults, elevated plasma p-tau181 is associated with future increased Aβ deposition across multiple brain regions. Our results highlight the potential utility of p-tau181 as a blood-biomarker to screen for brain-amyloid deposition in cognitively healthy individuals in a community-setting.
KW - Aβ-PET
KW - Dementia
KW - biomarkers
KW - brain positron emission tomography
KW - tau-PET
UR - http://www.scopus.com/inward/record.url?scp=85132280618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85132280618&partnerID=8YFLogxK
U2 - 10.3233/JAD-215639
DO - 10.3233/JAD-215639
M3 - Article
C2 - 35491781
AN - SCOPUS:85132280618
SN - 1387-2877
VL - 87
SP - 1517
EP - 1526
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -