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Role of Fluid Biomarkers and PET Imaging in Early Diagnosis and its Clinical Implication in the Management of Alzheimer's Disease.

ABSTRACT: Clinical diagnosis of Alzheimer's disease (AD) is based on symptoms; however, the challenge is to diagnose AD at the preclinical stage with the application of biomarkers and initiate early treatment (still not widely available). Currently, cerebrospinal fluid (CSF) amyloid-? 42 (A?42) and tau are used in the clinical diagnosis of AD; nevertheless, blood biomarkers (A?42 and tau) are less predictive. Amyloid-positron emission tomography (PET) imaging is an advancement in technology that uses approved radioactive diagnostic agents (florbetapir, flutemetamol, or florbetaben) to estimate A? neuritic plaque density in adults with cognitive impairment evaluated for AD and other causes of cognitive decline. There is no cure for AD to date-the disease progression cannot be stopped or reversed; approved pharmacological agents (donepezil, galantamine, and rivastigmine; memantine) provide symptomatic treatment. However, the disease-modifying therapies are promising; aducanumab and CAD106 are in phase III trials for the early stages of AD. In conclusion, core CSF biomarkers reflect pathophysiology of AD in the early and late stages; the application of approved radiotracers have potential in amyloid-PET brain imaging to detect early AD.

SUBMITTER: Hameed S

PROVIDER: S-EPMC7081089 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Role of Fluid Biomarkers and PET Imaging in Early Diagnosis and its Clinical Implication in the Management of Alzheimer's Disease.

Hameed Shahul S Fuh Jong-Ling JL Senanarong Vorapun V Ebenezer Esther Gunaseli M EGM Looi Irene I Dominguez Jacqueline C JC Park Kyung Won KW Karanam Ananda Krishna AK Simon Oliver O

Journal of Alzheimer's disease reports 20200212 1

Clinical diagnosis of Alzheimer's disease (AD) is based on symptoms; however, the challenge is to diagnose AD at the preclinical stage with the application of biomarkers and initiate early treatment (still not widely available). Currently, cerebrospinal fluid (CSF) amyloid-β 42 (Aβ<sub>42</sub>) and tau are used in the clinical diagnosis of AD; nevertheless, blood biomarkers (Aβ<sub>42</sub> and tau) are less predictive. Amyloid-positron emission tomography (PET) imaging is an advancement in tec ...[more]

PMID: 32206755

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Project description:ObjectiveWe analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls (HCs) and tested baseline CSF biomarkers for prediction of clinical decline in PD.MethodsAmyloid-β 1 to 42 (Aβ42 ), total tau (t-tau) and phosphorylated tau (p-tau) at the threonine 181 position were measured using the high-precision Roche Elecsys electrochemiluminescence immunoassay in all available CSF samples from longitudinally studied patients with PD (n = 416) and HCs (n = 192) followed for up to 3 years in the Parkinson's Progression Markers Initiative (PPMI). Longitudinal CSF and clinical data were analyzed with linear-mixed effects models.ResultsWe found patients with PD had lower CSF t-tau (median = 157.7 pg/mL; range = 80.9-467.0); p-tau (median = 13.4 pg/mL; range = 8.0-40.1), and Aβ42 (median = 846.2 pg/mL; range = 238.8-3,707.0) than HCs at baseline (CSF t-tau median = 173.5 pg/mL; range = 82.0-580.8; p-tau median = 15.4 pg/mL; range = 8.1-73.6; and Aβ42 median = 926.5 pg/mL; range = 239.1-3,297.0; p < 0.05-0.001) and a moderate-to-strong correlation among these biomarkers in both patients with PD and HCs (Rho = 0.50-0.97; p < 0.001). Of the patients with PD, 31.5% had pathologically low levels of CSF Aβ42 at baseline and these patients with PD had lower p-tau levels (median = 10.8 pg/mL; range = 8.0-32.8) compared with 27.7% of HCs with pathologically low CSF Aβ42 (CSF p-tau median = 12.8 pg/mL; range 8.2-73.6; p < 0.03). In longitudinal CSF analysis, we found patients with PD had greater decline in CSF Aβ42 (mean difference = -41.83 pg/mL; p = 0.03) and CSF p-tau (mean difference = -0.38 pg/mL; p = 0.03) at year 3 compared with HCs. Baseline CSF Aβ42 values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD.InterpretationOur data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, although modest over a 3-year period, suggest biomarker profiles in PD may deviate from healthy aging. ANN NEUROL 2020;88:574-587.

Dataset Information

Role of Fluid Biomarkers and PET Imaging in Early Diagnosis and its Clinical Implication in the Management of Alzheimer's Disease.

Publications

Role of Fluid Biomarkers and PET Imaging in Early Diagnosis and its Clinical Implication in the Management of Alzheimer's Disease.

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