Plasma Phospho-tau217in Alzheimer Disease (AD)
Alzheimer disease (AD) pathology starts with a prolonged phase of beta-amyloid (Abeta) accumulation without symptoms
- importance of this presymptomatic, or preclinical, stage has been reported by studies finding that Abeta measured by cerebrospinal fluid (CSF) biomarkers or positron emission tomography (PET) predicted cognitive decline in people who were cognitively unimpaired (CU)
- plasma P-tau217 predicted cognitive decline in patients with preclinical AD (1)
- findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments
- been shown that plasma P-tau217 differentiated clinically diagnosed AD dementia from other neurodegenerative disorders (2)
- also distinguished participants with neuropathologically defined AD from participants without diagnostic levels of AD histopathology
- plasma P-tau217 levels correlated with cerebral tau tangles and discriminated abnormal vs normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures
- a blood test based on the ratio of plasma phosphorylated tau 217 (p-tau217) relative to non–p-tau217 (expressed as percentage of p-tau217) combined with the amyloid-β 42 and amyloid-β 40 plasma ratio (the amyloid probability score 2 [APS2]) had high diagnostic accuracy for identifying Alzheimer disease among individuals with cognitive symptoms in primary and secondary care, providing superior performance compared with the diagnostic accuracy after standard clinical evaluation (3)
Revised criteria for diagnosis and staging of Alzheimer's disease has an emphasis on biological markers of AD (4):
- defined Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic
- progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms
- early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles)
- an abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum
- later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms
- an integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages
Reference:
- Mattsson-Carlgren N et al. Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers. JAMA Neurol. Published online February 06, 2023. doi:10.1001/jamaneurol.2022.5272
- Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, Su Y, Chen Y, Serrano GE, Leuzy A, Mattsson-Carlgren N, Strandberg O, Smith R, Villegas A, Sepulveda-Falla D, Chai X, Proctor NK, Beach TG, Blennow K, Dage JL, Reiman EM, Hansson O. Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA. 2020 Aug 25;324(8):772-781. doi: 10.1001/jama.2020.
- Palmqvist S, Tideman P, Mattsson-Carlgren N, et al. Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care. JAMA. Published online July 28, 2024. doi:10.1001/jama.2024.13855
- Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimer's Dement. 2024; 20: 5143–5169