Blood Biomarkers in Neurodegenerative Diseases

Blood-based biomarkers offer a major advance in the clinical evaluation of neurodegenerative diseases. Currently, research studies have reported robust assays of blood markers for the detection of amyloid and tau pathologies specific to Alzheimer disease (amyloid-β peptides, and p-tau) and nonspecific blood markers of neuronal (neurofilament light, β-synuclein, and ubiquitin-C-terminal-hydrolase-L1) and glial degeneration (glial fibrillary acidic protein) that can measure key pathophysiologic processes in several neurodegenerative diseases. In the near future, these markers may be used for screening, diagnosis, or disease and treatment response monitoring. Blood-based biomarkers for neurodegenerative diseases have been rapidly implemented in research, and they have the potential to enter clinical use soon in different clinical settings. In this review, we will describe the main developments and their potential implications for the general neurologist.

[1]  K. Blennow,et al.  Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays , 2022, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[2]  K. Blennow,et al.  Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease , 2022, Nature Medicine.

[3]  M. Carrillo,et al.  The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease , 2022, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[4]  C. Jack,et al.  Performance of plasma phosphorylated tau 181 and 217 in the community , 2022, Nature Medicine.

[5]  Suzanne E. Schindler,et al.  Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light , 2022, Neurology.

[6]  A. Danek,et al.  Serum Beta‐Synuclein Is Higher in Down Syndrome and Precedes Rise of pTau181 , 2022, Annals of neurology.

[7]  F. Barkhof,et al.  Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease , 2022, The Journal of Prevention of Alzheimer's Disease.

[8]  K. Blennow,et al.  The accuracy and robustness of plasma biomarker models for amyloid PET positivity , 2022, Alzheimer's research & therapy.

[9]  W. M. van der Flier,et al.  Association of the ATN Research Framework With Clinical Profile, Cognitive Decline, and Mortality in Patients With Dementia With Lewy Bodies , 2022, Neurology.

[10]  Sara C. LaHue,et al.  Hepatic and renal function impact concentrations of plasma biomarkers of neuropathology , 2022, Alzheimer's & dementia.

[11]  W. M. van der Flier,et al.  Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231 , 2021, Alzheimer's Research & Therapy.

[12]  G. Beligere,et al.  Evaluation of Acute Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 Plasma Levels in Traumatic Brain Injury Patients with and without Intracranial Lesions , 2021, Neurotrauma reports.

[13]  J. Clarimón,et al.  Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia , 2021, Translational Neurodegeneration.

[14]  K. Blennow,et al.  Characterization of pre‐analytical sample handling effects on a panel of Alzheimer's disease–related blood‐based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[15]  D. Reboussin,et al.  Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT) , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[16]  F. Schmitt,et al.  Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down syndrome: a cohort study , 2021, The Lancet Neurology.

[17]  A. Toga,et al.  Characterizing plasma NfL in a community‐dwelling multi‐ethnic cohort: Results from the HABLE study , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[18]  K. Blennow,et al.  Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome , 2021, Nature Communications.

[19]  K. Blennow,et al.  Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias , 2021, Journal of Neurology, Neurosurgery, and Psychiatry.

[20]  John K. Yue,et al.  Comparison of GFAP and UCH-L1 Measurements from Two Prototype Assays: The Abbott i-STAT and ARCHITECT Assays , 2021, Neurotrauma reports.

[21]  W. M. van der Flier,et al.  Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology , 2020, Alzheimer's Research & Therapy.

[22]  K. Blennow,et al.  Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease , 2020, Translational Psychiatry.

[23]  K. Blennow,et al.  Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration. , 2020, Journal of Alzheimer's disease : JAD.

[24]  H. Hampel,et al.  Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases , 2020, Molecular Neurobiology.

[25]  K. Blennow,et al.  Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. , 2020, JAMA.

[26]  Nick C Fox,et al.  Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study , 2020, Molecular Psychiatry.

[27]  K. Blennow,et al.  Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum , 2020, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[28]  S. Lehmann,et al.  Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study , 2020, The Lancet.

[29]  K. Blennow,et al.  Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts , 2020, The Lancet Neurology.

[30]  K. Blennow,et al.  Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia , 2020, Nature Medicine.

[31]  J. Diehl-Schmid,et al.  Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer's Disease. , 2020, Journal of proteome research.

[32]  J. Karlawish,et al.  Cognitively unimpaired adults’ reactions to disclosure of amyloid PET scan results , 2020, PloS one.

[33]  Nick C Fox,et al.  Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study , 2019, The Lancet Neurology.

[34]  Philip S. Insel,et al.  Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease , 2019, EMBO molecular medicine.

[35]  James G. Bollinger,et al.  High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis , 2019, Neurology.

[36]  N. Martin,et al.  Dimethyl fumarate decreases neurofilament light chain in CSF and blood of treatment naïve relapsing MS patients , 2019, Journal of Neurology, Neurosurgery, and Psychiatry.

[37]  K. Blennow,et al.  Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. , 2019, JAMA neurology.

[38]  A. Ludolph,et al.  CNS phenotype in X linked Charcot- Marie-Tooth disease , 2018, Journal of Neurology Neurosurgery & Psychiatry.

[39]  C. Jack,et al.  Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography , 2018, Alzheimer's & Dementia.

[40]  C. Rowe,et al.  High performance plasma amyloid-β biomarkers for Alzheimer’s disease , 2018, Nature.

[41]  T. Tokuda,et al.  Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome , 2017, Molecular Neurodegeneration.

[42]  K. Blennow,et al.  Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis , 2017, The Lancet Neurology.

[43]  K. Fliessbach,et al.  Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias , 2017, Neurology.

[44]  K. Blennow,et al.  Plasma neurofilament light chain predicts progression in progressive supranuclear palsy , 2016, Annals of clinical and translational neurology.

[45]  A. Nakamura,et al.  Novel plasma biomarker surrogating cerebral amyloid deposition , 2014, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[46]  Ludwig Kappos,et al.  Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases , 2013, PloS one.

[47]  D. Perl,et al.  Role of the neuropathology of Alzheimer disease in dementia in the oldest-old. , 2008, Archives of neurology.