Abstract
A combination of plasma phospho-tau (P-tau) and other accessible biomarkers might provide accurate prediction about the risk of developing Alzheimer's disease (AD) dementia. We examined this in participants with subjective cognitive decline and mild cognitive impairment from the BioFINDER (n = 340) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 543) studies. Plasma P-tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and an AD-specific magnetic resonance imaging measure were examined using progression to AD as outcome. Within 4 years, plasma P-tau217 predicted AD accurately (area under the curve (AUC) = 0.83) in BioFINDER. Combining plasma P-tau217, memory, executive function and APOE produced higher accuracy (AUC = 0.91, P < 0.001). In ADNI, this model had similar AUC (0.90) using plasma P-tau181 instead of P-tau217. The model was implemented online for prediction of the individual probability of progressing to AD. Within 2 and 6 years, similar models had AUCs of 0.90-0.91 in both cohorts. Using cerebrospinal fluid P-tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy significantly. The clinical predictions by memory clinic physicians had significantly lower accuracy (4-year AUC = 0.71). In summary, plasma P-tau, in combination with brief cognitive tests and APOE genotyping, might greatly improve the diagnostic prediction of AD and facilitate recruitment for AD trials.
Highlights
Determining if a patient with subtle cognitive symptoms, such as memory decline, suffers from prodromal or preclinical Alzheimer’s disease (AD) and will progress to AD dementia within the near future remains a challenge for clinicians
One hundred and sixty-four patients were subsequently characterized as having subjective cognitive decline (SCD), and 176 patients were subsequently characterized as having mild cognitive impairment (MCI)
Ninety-one patients progressed to AD dementia at follow-up; 48 patients progressed to other dementias; and 201 patients did not progress to any dementia
Summary
Determining if a patient with subtle cognitive symptoms, such as memory decline, suffers from prodromal or preclinical AD and will progress to AD dementia within the near future remains a challenge for clinicians. A possible turning point has emerged with the recent development of blood-based biomarkers, making it possible to measure NfL10,11, Aβ42/Aβ40 In the clinical workup of patients with cognitive complaints, it is unlikely that plasma P-tau (or any other biomarker) will achieve the highest potential predictive accuracy on its own, owing to the multifactorial nature of AD etiology and its heterogenous clinical presentation. There is, a need to identify which other measures plasma P-tau should be combined with to produce the most accurate prediction of future AD and establish an optimal diagnostic algorithm of non-invasive, cost-effective and available methods for early diagnosis of AD
Sign-in/Register to view highlights & summary 
Submitted Version (
Free)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
