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A simple test combination for identifying early Alzheimer’s disease
Many people experience mild cognitive decline, but what is their risk of developing Alzheimer’s disease within 4 years? One blood sample to test for phospho-tau and APOE genotype combined with one memory test and two executive function tests carried out in primary care can provide a prediction of the risk with an accuracy (area under the curve) of 0.91, said Professor Oskar Hansson, Lund University, Sweden at ADPD2022.
Biomarkers are used to diagnose Alzheimer’s disease (AD), to select individuals with preclinical disease for clinical trials, and to identify subgroups of patients who might respond differently to different therapies, explained Professor Hansson.
Identification of patients with preclinical Alzheimer’s disease is challenging in primary care
Specialist techniques for detecting amyloid beta and tau
Most patients with mild cognitive decline present in primary care, but an accurate prediction of future Alzheimer’s disease (AD) has required specialist intervention for:
- Positron emission tomography (PET) to detect amyloid beta (Aβ) accumulation2
- Lumbar puncture to detect cerebrospinal fluid (CSF) Aβ42/Aβ40 or Aβ42/phospho-tau (p-tau) ratios3
The concordance between Aβ PET and CSF Aβ42 ratios is high,4 said Professor Hansson, and PET also provides information on the location of Aβ.
Blood-based techniques for detecting amyloid beta and tau
Blood-based biomarkers promise to improve diagnostic accuracy in primary care
Many blood-based Aβ42/Aβ40 tests have been developed to improve diagnostic accuracy in primary care. However, a head-to-head comparison of eight plasma Aβ42/Aβ40 assays for identifying early AD carried out by Professor Hansson and his team has revealed varying precision, with areas under the curve (AUCs) ranging from 0.64 to 0.84.5 It is therefore important to know which blood-based immunoassay is used in any clinical trial.
Another blood-based biomarker test — for p-tau — is now emerging as a diagnostic and prognostic biomarker of AD with potential use in clinical practice and for selecting people with preclinical AD for clinical trials,6 said Professor Hansson:
Plasma p-tau is increased in preclinical AD
- Plasma p-tau levels are increased by 500–700% in AD dementia7
- The ability of plasma p-tau to differentiate AD from non-AD is similar to that of CSF p-tau and tau-PET7
- Among non-demented individuals, abnormal levels of plasma p-tau at baseline are linked to the later development of AD dementia8
A blood and cognitive test combination for detecting early Alzheimer’s disease in primary care
Professor Hansson and his team have investigated whether the precision of plasma p-tau for detecting early AD might be improved by combining it with other simple tests for use in primary care.
The precision of the combination of plasma p-tau, APOE genotyping, and brief cognitive tests is similar to that of CSF biomarker-based algorithms
They found that combining the results of plasma p-tau, APOE genotyping, and brief cognitive tests for memory and executive function could predict the development of dementia within 4 years with an AUC of 0.91.9
Furthermore, not only is this combination of simple tests practicable for use in primary care, it also provides:
- Similar precision as CSF biomarker-based algorithms
- Significantly better precision than a prediction by experts based on clinical assessment9
Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.
References
- Hansson O. Biomarkers for neurodegenerative diseases. Nat Med 2021;27:954–63.
- Clark CM, et al. Use of florbetapir-PET for imaging β-amyloid pathology. JAMA 2011;305:275–283.
- Janelidze S, et al. Concordance between different amyloid immunoassays and visual amyloid positron emission tomographic assessment. JAMA Neurol 2017;74:1492–1501.
- Hansson O, et al. CSF biomarkers of Alzheimer’s disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement 2018 ;14:1470–81.
- Janelidze S, et al. Head-to-head comparison of 8 plasma amyloid-β 42/40 assays in Alzheimer disease. JAMA Neurol 2021;78:1375–82.
- Janelidze S, et al. Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis,neuropathology and longitudinal progression to Alzheimer's dementia. Nat Med 2020 Mar;26(3):379–86.
- Palmqvist S, et al. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA 2020;324:772–81.
- Janelidze S, et al. Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia. Nat Med 2020;26:379–86.
- Palmqvist S, et al. Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures. Nat Med 2021;27:1034–42.